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Applied Animal Behaviour Science (2008) Volume 112: 1-32
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doi: 10.1016/j.applanim.2008.02.007
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Final Revision – NOT EDITED by the journal
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What is it like to be a rat? Rat sensory perception and its
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implications for experimental design and rat welfare
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Charlotte C. Burn
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Department of Clinical Veterinary Science, University of Bristol, Bristol BS40 5DU,
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UK
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Running title: Rat sensory perception and its implications
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Correspondence address: Department of Clinical Veterinary Science, University of
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Bristol, Bristol BS40 5DU, UK
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Abstract
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This review of rat sensory perception spans eight decades of work conducted across
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diverse research fields. It covers rat vision, audition, olfaction, gustation, and
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somatosensation, and describes how rat perception differs from and coincides with
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ours. As Nagel’s seminal work (1974) implies, we cannot truly know what it is like to
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be a rat, but we can identify and acknowledge their perceptual biases. These primarily
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nocturnal rodents are extremely sensitive to light, with artificial lighting frequently
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causing retinal degeneration, and their vision extends into the ultraviolet. Their
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olfactory sensitivity and ultrasonic hearing means they are influenced by
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environmental factors and conspecific signals that we cannot perceive. Rat and human
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gustation are similar, being opportunistic omnivores, yet this sense becomes largely
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redundant in the laboratory, where rodents typically consume a single homogenous
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diet. Rat somatosensation differs from ours in their thigmotactic tendencies and highly
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sensitive, specialised vibrissae. Knowledge of species-specific perceptual abilities can
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enhance experimental designs, target resources, and improve animal welfare.
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Furthermore, the sensory environment has influences from neurone to behaviour, so it
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can not only affect the senses directly, but also behaviour, health, physiology, and
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neurophysiology. Research shows that environmental enrichment is necessary for
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normal visual, auditory, and somatosensory development. Laboratory rats are not
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quite the simple, convenient models they are sometimes taken for; although very
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adaptable, they are complex mammals existing in an environment they are not
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evolutionarily adapted for. Here, many important implications of rat perception are
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highlighted, and suggestions are made for refining experiments and housing.
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Keywords: Animal Welfare; Communication; Olfaction; Perception; Rats;
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Refinement; Vision
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The stimuli that an animal can perceive depend on the available sensory apparatus,
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while the way stimuli are evaluated in terms of their biological relevance depends on
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the animal’s innate biases, cognitive abilities and experiences. Perception is therefore
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a subjective distortion of reality, differing between species and even between
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individuals within a species. Since rats and mice, which have similar perceptual
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abilities to each other, constitute over 80% of all research animals in the European
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Union (Commission of the European Communities, 2003), and they have been bred
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for research since the late 1800s (Krinke, 2000; Whishaw & Kolb, 2005), much is
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known about their perceptual biases. However, the information is scattered through
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time and across different research fields, so it is not easily available to researchers, rat
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caretakers, and other rat specialists. The resulting lack of awareness can have
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serious implications, sometimes leading to poorly designed experiments and harming
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rat welfare. This review brings current information together, to help inform and refine
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rodent experiments and housing.
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Introduction
The review concentrates on the laboratory rat, Rattus norvegicus, since
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summaries of mouse sensory perception are included within several other review
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papers (Sherwin, 2002; Olsson et al., 2003; Latham & Mason, 2004). Much of the
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information will also be true for mice and other rodents, but care should still be taken
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if extrapolating between species. The species’ natural ecology – such as whether they
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are diurnal or nocturnal, social or solitary, arboreal, burrowing or terrestrial – will
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profoundly affect their sensory perception. These ethological considerations are
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highly relevant in laboratory rats despite their domestication; adult laboratory rats
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retain so many of their wild instincts that, when released into a naturalistic habitat,
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their resulting community and behaviour rapidly resembles that of their wild relatives
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(Berdoy, 2002). This review is organised around the classic ‘five senses’: vision, audition,
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olfaction, gustation and somatosensation. It should be remembered that these are
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actually not the only senses; indeed rats may even possess a magnetic compass, like
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mice (Muheim et al., 2006) and hamsters (Deutschlander et al., 2003), but most
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published information currently covers the aforementioned five senses. For each
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sense, the rat’s sensory biases relative to humans are first described, then some
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practical implications of its perception with respect to welfare and experimental
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design are discussed. This is an applied review, focussing on the known or suspected
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implications of each sense, and aiming to provide enough information to allow readers
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to extrapolate to their own situations. The review cannot be completely
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comprehensive, and it will become clear that in many cases, rat sensory perception is
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still poorly understood.
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2
Vision
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An obvious difference between human and rat vision is that rats’ eyes are
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located on the sides of their heads, rather than the front. They therefore have a wider
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field of view, but less binocular overlap than us: wild rats have a binocular overlap of
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35o, domestic rats 76o, and humans 105o (Heffner & Heffner, 1992a).
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Wild rats usually inhabit burrows or other enclosed environments, and tend to
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be nocturnal or crepuscular, so most of their activities occur under low light
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conditions (e.g. Calhoun, 1963). Consequently, rats rely relatively little on vision, but
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they are dramatically more sensitive to dim light than we are, able to discriminate tiny
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increments in intensity, indiscernible to us, including discriminating ‘total
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darkness’ from 0.107 lux (Campbell & Messing, 1969).
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Rats, especially albinos, have much poorer visual acuity (Lashley, 1938; Creel
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et al., 1970; Prusky et al., 2002) and narrower depth perception than humans
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(O'Sullivan & Spear, 1964; Routtenberg & Glickman, 1964). For example, human
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acuity can be around 30 c/d (‘cycles per degree’ – a measure of spatial resolution
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accounting for stimulus size and distance), while pigmented rats’ acuities are only 1–
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1.5 c/d and albino strains have even lower acuities of 0.5 c/d (Prusky et al., 2002).
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This presumably gives an extremely blurred image by human standards (Figure 1,
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reprinted from Prusky and colleagues, 2002). Poor acuity in rats is probably partly
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due to their eyes’ relatively small size, and partly because their eyes appear to
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have very limited abilities to focus light from different distances or angles
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compared with human eyes (Artal et al., 1998). Rats often bob their heads which
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may help them gain motion cues about the distance of objects (Legg & Lambert,
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1990).
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Experiments in the 1930s suggested that, contrary to popular belief, rats possess
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colour vision (e.g. Munn & Collins, 1936; Walton & Bornemeier, 1938), which has
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recently been confirmed through electroretinograms and quantitative behavioural tests
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(Jacobs et al., 2001). Rod cells comprise 99% of rat photoreceptors, but rats also have
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two cone cell types (Szel & Rohlich, 1992). Around 93% of the cones respond
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maximally to blue–green light (around 510 nm), while the remaining 7% respond to
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ultraviolet (UV) (around 360 nm) (Jacobs et al., 2001; Akula et al., 2003). Cone
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responses are normally distributed, so rats actually perceive hues ranging from
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ultraviolet (400 nm) to orange-red (around 635 nm) (Jacobs et al., 2001), but they are
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most responsive to colours near their peak sensitivities (Jacobs et al., 2001; Akula et
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al., 2003).
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Flicker fusion thresholds (when emitted light flickers rapidly enough to appear
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constant) for rats are not yet known, but are relevant for their perception of video
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images and artificial lighting (D'Eath, 1998). Flicker fusion thresholds decrease with
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high light intensity, and increase with fatigue. Animals with high proportions of rod 5
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cells, like rats, generally have high flicker fusion thresholds, so rats might perceive
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videos, computer monitors, and some fluorescent lighting as flickering (Jarvis et al.,
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2003).
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Discussion of the implications of rat vision is separated according to sensitivity
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to light generally, colour vision, periodicity, and acuity.
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2.1
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The sensitivity of rats to light (Campbell & Messing, 1969) means that light levels
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comfortable for humans can rapidly cause retinal atrophy (reviewed in Schlingmann
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et al., 1993a; Schlingmann et al., 1993b) and cataract formation in rats (Rao, 1991).
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Albinos are particularly susceptible because they lack protective melanin in the iris
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and retinal epithelium, and the entire eyeball is slightly transparent (Schlingmann et
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al., 1993b). Consequently, even when the iris contracts in bright light, most of the
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light still enters the eye (Williams et al., 1985). In fact, albino rats may be the most
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susceptible of all laboratory animals to light-induced retinal degeneration (Bellhorn,
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1980).
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Sensitivity to light
To illustrate the relevant range of light intensities, the UK code of practice for
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the care and use of laboratory animals suggests that “350–400 lux at bench level is
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adequate for routine experimental and laboratory activities” (Home Office, 1989).
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Light intensities within cages are commonly between about 150 and 550 lux
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(Schlingmann et al., 1993c), but are higher in laboratory rooms, with upper limits
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approaching 10,000 lux due to current technological limitations (e.g. Light Therapy
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ProductsTM, 2006; Outside In Ltd., 2006). Humans can tolerate still higher intensities
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– outdoors on sunny days light often exceeds 50,000 lux, and only at this order of
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magnitude are discomfort and potential retinal damage likely in humans.
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Light intensities of only 65 lux can cause retinal degeneration in albino rats,
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even on a 12 h light-dark cycle (Semple-Rowland & Dawson, 1987). Half the
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photoreceptors were permanently damaged after just 3 days at 133 lux in albinos, but 6
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pigmented rats were less susceptible, with equivalent damage occurring at 950 lux
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(Williams et al., 1985). Rod cells are particularly vulnerable to light destruction, but
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cones often survive even after all rods have been destroyed (Cicerone, 1976; La Vail,
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1976). Long-term cyclical light intensities of about 500 lux within an animal room
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can also cause cataracts in albino rats (Rao, 1991). These problems are worst in rats
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housed closest to the light source, usually those highest in the rack (Rao, 1991; Perez
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& Perentes, 1994).
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Surprisingly, some vision can remain after constant long-term light exposure,
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even when no intact photoreceptor cells can be observed (e.g. Lemmon & Anderson,
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1979). This might be conferred by a few remaining cones that may be so sparse that
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they were undetectable by the quantitative techniques used (Cicerone, 1976; La Vail,
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1976). Even so, under ‘ordinary’ laboratory conditions, visual impairments can
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confound some tests. For example, in the Morris water maze – a test of cognitive
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function – rats with incidental light-induced retinal damage perform as poorly as rats
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with cognitive deficits, both groups displaying difficulties locating the platform
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(Osteen et al., 1995; Lindner et al., 1997). Also, in commonly used ‘anxiety’ tests,
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such as open field tests and light-dark boxes, visually impaired individuals might
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venture into the exposed/light areas more than fully sighted ones, through their lesser
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ability to discriminate light from dark, but this requires experimental confirmation.
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Therefore, light-induced retinopathy should be controlled for in such tests, or non-
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visual tests used alongside the established visual ones.
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Welfare problems might arise at even lower light levels than those causing
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retinal damage, because of motivation to hide, as well as to avoid ocular discomfort
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(Schlingmann et al., 1993c). Rats, especially albinos, reliably choose the lowest light
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intensities available, even when all the choices are very dim, appearing
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indistinguishable to humans (Campbell & Messing, 1969; Woodhouse & Greenfeld,
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1985; Blom et al., 1995). Rats’ aversion to light was clearly demonstrated in a study
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showing that sleeping pigmented and albino rats awoke and moved to areas of lower 7
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illumination at thresholds of only 60 and 25 lux, respectively (Schlingmann et al.,
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1993c). Consistent with such behaviour, chromodacryorrhoea, an aversion-related
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secretion from the Harderian gland (e.g. Mason et al., 2004), increases with brighter
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light (Hugo et al., 1987).
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There is clearly a conflict between human workers needing adequate light to
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inspect rats, for example for signs of illness, and rats needing to avoid damaging or
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aversive light levels. Schlingmann (1993a) therefore stresses the importance of
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providing shelters within cages, allowing rats some control over their light exposure.
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As described below, coloured shelters exist that allow humans to see rodents, while it
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supposedly appears dark to the rodents inside the shelter, although their efficacy
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requires confirmation.
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Light levels affect commonly used psychological tests, such as elevated plus-
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mazes in which exploration of the exposed arms is taken to indicate reduced anxiety;
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rats explore the exposed arms more in dim than bright light (Cardenas et al., 2001;
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Garcia et al., 2005). Moreover, some effects are only found under certain light
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conditions. For example, the anxiolytic effects of gentling only emerge in brightly lit
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open fields (Hirsjarvi & Valiaho, 1995), and some drug effects are influenced by plus
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maze illumination (Clenet et al., 2006). Therefore, some control and careful
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description of lighting conditions during these tests is necessary to account for its
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influence on psychological measures.
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Surgery presents a difficult situation because good lighting is essential for
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delicate operations, but the anaesthetised, unblinking rat is unable to protect its eyes
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from that light. Care should therefore be taken, not only to keep the eyes hydrated, but
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also to protect them from prolonged bright light. Interestingly, the anaesthetic agent,
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halothane, prevents retinal degeneration (Keller et al., 2001); other anaesthetics have
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not yet been investigated. This protection is afforded under white, but not blue, light.
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Despite the above evidence that bright light is harmful to rats, this aspect of
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their biology is not always considered in some fields of research. An example is the
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use of rats as models for seasonal affective disorder in humans, exploring whether
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bright light therapy (up to 11,500 lux for 2 weeks) can cure depression in rats (e.g.
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Dilsaver & Majchrzak, 1988; Giroux et al., 1991; Humpel et al., 1992; Overstreet et
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al., 1995). Unsurprisingly, the depression was not cured, and the one study that
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considered the effects of light on rat vision discovered massive destruction of the
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albinos’ photoreceptors (Humpel et al., 1992). These examples illustrate how crucial
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knowledge of species-specific perception is for generating reasonable hypotheses and
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preventing animal suffering.
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2.2
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Rats are not colour-blind (Muenzinger & Reynolds, 1936; Munn & Collins, 1936;
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Walton & Bornemeier, 1938; Lemmon & Anderson, 1979; Jacobs et al., 2001).
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However, relative to humans, they perform poorly when discriminating between
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colours of similar wavelengths (Walton, 1933), and they take longer to learn colour
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discriminations than light intensity ones (Jacobs et al., 2001).
Colour vision
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To discuss the implications of rats’ colour sensitivity, the implications for
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emitted light and that reflected by objects in the environment will be dealt with
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separately, as their effects are quite distinct.
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2.2.1
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Standard artificial lighting rarely emits UV wavelengths (e.g. Bellhorn, 1980; Latham
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& Mason, 2004), since human cones are insensitive to it. To date, no studies have
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apparently investigated the effects of UV-deficient light on rats. In some birds, UV
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light is important for their welfare (Moinard & Sherwin, 1999; Maddocks et al., 2001)
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and normal behaviour (Bennett & Cuthill, 1994), but laboratory mice appear to have,
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if anything, a slight aversion to it (C. M. Sherwin, personal communication). Also,
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high levels of UV can cause cataracts in mice (in Bellhorn, 1980), and can affect
Emitted light
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reproductive and circadian rhythms in rats (reviewed in Brainard et al., 1994). In fact,
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the colour composition of artificial light can have large effects. In rats, blue light
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(around 490 nm) causes most retinal degeneration (reviewed in Schlingmann et al.,
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1993b), and also more disruption to fertility (Tong & Goh, 2000) than any other
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wavelengths tested; UV light was not included in these studies, but is of a shorter
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wavelength than blue light so may be more harmful.
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At the opposite end of the spectrum, dim red light is sometimes used to observe
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nocturnal behaviour in rats, because it is on the upper edge of the wavelengths visible
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as colour to them (Jacobs et al., 2001). However, rats’ rod cells are stimulated by
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similar wavelengths to human rod cells, including red light (Akula et al., 2003). This
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means that, provided some rod cells remain intact, rats can see red light, even if only
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as light and dark contrast. This may not be a problem in experiments if rats are
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habituated to it, since moonlight would provide illumination in the wild. As an
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alternative to red light, sodium lamps, which emit very narrow peaks of yellow–
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orange (589 and 589.6 nm) light, can be used (McLennan & Taylor-Jeffs, 2004). Not
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only is it more visible to humans than red light, but there were no long-term
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differences between the activity levels of mice when illuminated by this lamp or in
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darkness. However, in studies unequivocally requiring rats to behave as if in pitch
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darkness, infra-red light and the necessary viewing equipment should be used.
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It is also worth noting that most video equipment and computer monitors, which
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create images using emitted light, include no UV emissions and the colour balance is
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optimised for human vision (D'Eath, 1998). Even in black-and-white images and light
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from white artificial light bulbs, ‘white’ is composed of red, green and blue light
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adjusted for humans, and so would not appear as white to rats. Therefore, any such
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images presented to species with different colour sensitivities, particularly UV-
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sensitive animals, could lack important information.
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2.2.2
Colour in the environment
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Caution is required when presenting images to rats in discrimination tests, even if the
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cues reflect rather than emit light. Different inks have different spectral properties that
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may be invisible to the human eye, and some might even reflect UV. Moreover,
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different pigments might differ in their olfactory qualities, which could be more
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salient to rats than their visual qualities. Even if this does not harm the experimental
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purpose, it can make standardisation between experiments difficult.
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Outside experimental situations, there are also some relevant implications of
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rodent colour vision within the homecage. In recent years, manufacturers of rodent
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environmental enrichments have produced transparent shelters in various colours (e.g.
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Robbins, 2004; Datesand Ltd, 2005). The idea behind them is that, while rodents -
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supposedly blind to the shelter’s colour - perceive themselves as being sheltered in a
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dark environment, human carers can inspect them without disturbing them. However,
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these shelters seem not to have been independently evaluated for their efficacy. Red
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transparent material might make a suitable shelter, being the least visible colour to
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rats (Jacobs et al., 2001), but as explained earlier, it would still stimulate rod cells and
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possibly some cones. The colour of the homecage itself might also affect rats. Sherwin and Glen
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(2003) housed mice in different coloured cages and found that they had significantly
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different preferences for cage-colours. Moreover, the colour affected their food-to-
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body mass conversion rates and their elevated plus-maze anxiety. Assuming these
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effects were due to the colours directly (rather than the scents, tastes, or textures of the
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dyes used), this study shows that environmental colour can have surprisingly strong
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effects on mouse behaviour and physiology, and so possibly that of rats too.
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2.3
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Rats tend to be most active at dusk and dawn, although their circadian rhythms are
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relatively flexible (e.g. Calhoun, 1963). Because we are diurnal, many rodent
Periodicity
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experiments are carried out in the light, so much of our knowledge of this species
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comes from individuals awakened during their resting period, and tested under much
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brighter conditions than they would voluntarily experience. The implications of this
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can be profound, but time-shifted experiments are still rare in some fields. The brain
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state changes radically between sleep and activity, with whole populations of neurons
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shifting between activity and inactivity (Hobson, 2005; Saper et al., 2005). The time
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of testing can strongly influence the variables of interest in experiments. For example,
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during the light phase, rats’ cardiovascular responses to various stressors are more
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pronounced (Schnecko et al., 1998), and they show less exploratory behaviour in an
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elevated plus-maze than in the dark phase (Andrade et al., 2003).
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For most experiments, rats will be in a wakeful state provided they have
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sufficient time to awaken, but little published information is available on how long
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rodents require to fully awaken (i.e. be in the same state as during the active phase).
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Any conclusions drawn from light phase studies of rats as human models could suffer
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from interpretive problems, because it is unclear whether the observed state would
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reflect a similar state in our light (active) phase or our (dark) resting phase.
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Time shifted experiments and husbandry can be made possible by using red or
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sodium illumination as described above, and also by feeding rats only during the
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phase when we wish them to be active (cited in Saper et al., 2005); a situation that
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sometimes occurs in the wild (Calhoun, 1963).
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2.4
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As described above, rats have very poor acuity (Figure 1). Their image resolution is at
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least 20 times poorer than ours (Artal et al., 1998). Note though that the studies
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investigating rat visual acuity (Lashley, 1938; Creel et al., 1970; Artal et al., 1998;
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Robinson et al., 2001; Prusky et al., 2002) have used laboratory rats, whose acuity
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might have been further reduced by their artificially lit environments.
Acuity
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Apart from the damaging effects of light itself, several other factors can affect
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rat vision, including the early environment. Complete lack of light impairs rats’ visual
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development (Fagiolini et al., 1994), but providing environmental enrichment to these
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dark-reared animals can eliminate this effect (Bartoletti et al., 2004). In mice,
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enriched environments during rearing accelerate visual development and improve
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adult acuity (Prusky et al., 2000; Cancedda et al., 2004).
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Also, diet has a large influence on vision (Berson, 2000). For example, caloric
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restriction can prevent cataracts (e.g. Wolf et al., 2000), and antioxidant intake and
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consumption of certain vitamins can prevent retinal damage (Li et al., 1985; Berson,
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2000). Dietary composition is discussed in more detail in the Gustation section of this
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paper.
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The research implications of rats’ poor visual acuity depends on the experiment
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in question, but if visual cues are used they should be relatively large and high
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contrast, but not too bright as to be aversive. Also, visual cues may not be as salient to
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rats as cues in other modalities. Few experiments have tested this directly, but rats do
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remember auditory associations for longer than equivalent visual ones (Wallace et al.,
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1980), and can more rapidly learn discriminations using multimodal stimuli (floor
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surfaces differing in appearance, smell, and texture Dymond, 1995; Dymond et al.,
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1996) or olfactory or tactile cues (Birrell & Brown, 2000). However, vision is often
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the most appropriate sense for guiding rats in water mazes (Prusky & Douglas, 2005),
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for comparison with past studies, and for certain models of human activities.
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3
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Sound can be described in terms including its frequency, intensity, timbre (frequency
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spectrum) and envelope (shape of sound pressure through time). While young
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humans hear frequencies from about 0.02 kHz to 20 kHz (Moore, 2003), hearing in
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rats is shifted upwards to include the ultrasonic range (Kelly & Masterton, 1977). The
Audition
13
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lowest frequency rats have been reported to hear is 0.25 kHz and the highest is 80 kHz
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(Kelly & Masterton, 1977; Heffner & Heffner, 1992b; Heffner et al., 1994). They can
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also detect lower sound frequencies (Petounis et al., 1977), probably through contact
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with vibrating surfaces, and can even perceive low frequency sounds using their
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vibrissae (Neimark et al., 2003) (see the section on Somatosensation). Auditory sensitivity decreases near the extremes of the detectable frequencies,
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so sounds at the lower and higher extremes must be louder before rats can detect
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them. The rat’s peak sensitivity is estimated to lie between about 8 and 50 kHz (Kelly
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& Masterton, 1977; Heffner & Heffner, 1992b), although estimates vary, probably
347
due to factors including strain, age, and background noise. Even whether the
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homecages of rats are barren or environmentally enriched can greatly affect hearing
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sensitivity; auditory neurone performance is vastly improved by environmental
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enrichment (Engineer et al., 2004).
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The implications of rat auditory perception include what sound characteristics
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are harmful, vocal communication between rats, perception of the human voice, and
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experimental use of sound cues. There has also been debate about whether rats can
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echolocate.
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3.1
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Interactions between sound intensity and frequency (Fleshler, 1965; Voipio et al.,
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1998; Björk et al., 2000) make it difficult to determine detection- and safety-
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thresholds for sound intensities. The decibel (dB) scale is logarithmic, so even small
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numerical increases represent large increases in the actual intensity. European
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Union legislation (2003) states that advice and hearing-protection must be provided
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for human workers frequently exposed to sounds of 80 dB or more. Above about 150
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dB, auditory damage is inevitable with most perceivable sounds (Gamble, 1982).
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Equivalent thresholds are unknown for rats, but young rats are more sensitive to
Audiogenic damage in the laboratory
14
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sounds than older ones, and permanent audiogenic damage is most likely in pups
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between about 12 and 22 days of age (Voipio, 1997).
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In the laboratory, audible sounds as loud as 80–90 dB have been recorded; and
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50–75 dB for ultrasound (Milligan et al., 1993), so conceivably, audiogenic damage
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could occur in both humans and rats. Husbandry procedures cause the loudest sounds,
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especially if metallic equipment is involved (Gamble & Clough, 1976; Milligan et al.,
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1993; Sales et al., 1999). Filling metal food hoppers made 80 dB of (mostly
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ultrasonic) sound, which would occur about once a week for the rats’ lifetimes (Sales
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et al., 1999). This was measured from a distance of 50 cm, approximately the furthest
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that a caged rat could get from the sound.
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Many apparently silent activities or devices actually produce high levels of
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ultrasound (Sales et al., 1988; Sales et al., 1999). Examples include computer
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monitors, making 68–84 dB of broadband ultrasound (Sales et al., 1988), and some
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fluorescent lighting (G. J. Mason personal communication, and personal observation).
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Cage washers, hoses, running taps, squeaky chairs, and rotating glass stoppers (Sales
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et al., 1988) produce both ultrasound and audible sound, as do some air-flow hoods
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worn to prevent allergy in human workers (Picciotto et al., 1999). Similarly, standard
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fire alarms produce loud high and low frequency sounds, which laboratory animals
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cannot escape, so laboratories can be fitted with fire alarms that only emit sound
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audible to humans but not rodents (Home Office, 1989); although note that even
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frequencies below rats’ audible range can affect them (Petounis et al., 1977).
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Whether common laboratory sounds affect rodent welfare has not been
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investigated directly, but loud noises generally can trigger seizures, reduce fertility,
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and cause diverse metabolic changes (Sales et al., 1988; Milligan et al., 1993).
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Repeated short bursts of 2 kHz sound at 120 dB caused ‘behavioural despair’ in rats
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(Bulduk & Canbeyli, 2004). Longer-lasting sounds can also affect animals, although
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that has apparently not been tested in rats. In pigs, 90 dB prolonged or intermittent
15
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broadband noise increased cortisol, ACTH, noradrenaline:adrenaline ratios and time
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lying down, and decreased growth and social interactions (Otten et al., 2004).
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Conceivably then, a fluorescent light emitting loud ultrasound could cause significant
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stress in rats housed near it. The envelopes and timbres of sounds also determine how aversive or damaging
395 396
they are. Noise-type sounds, e.g. white noise or the sound of tearing paper, cause
397
stronger fear reactions in rats than equivalent harmonic or pure tones, or audible rat
398
vocalisations (Voipio, 1997). Sudden sounds are probably also more startling than
399
those with gradual onsets. It should be noted that avoidance of sound occurs at still
400
lower thresholds than those causing startle reactions (in Fleshler, 1965), or physical
401
damage.
402
Ultrasound detectors (e.g. bat detectors), which represent ultrasounds in a form
403
that humans can hear or visualise, would be useful as standard pieces of laboratory
404
equipment to regularly check whether ultrasound of certain frequencies is being
405
emitted in the animal rooms and to test experimental set-ups. Few experimenters
406
would choose to carry out experiments during loud building work, for example,
407
because of potential effects on the animals’ performances, and the same
408
meticulousness should apply to ultrasound. Indeed, background noise levels during
409
behavioural experiments do affect the apparent learning abilities of rats, with louder
410
white noise leading to faster completion of a maze task (Prior, 2006). Moreover, even
411
loud infrasound affects rat behaviour, reducing their activity and triggering sleep
412
(Petounis et al., 1977).
413
3.2
414
As well as audible ‘squeaks’, rats produce at least three types of ultrasonic
415
vocalisations. Firstly, juvenile rats produce a 40–50 kHz vocalisation (Noirot, 1968),
416
which together with olfactory cues, causes pup-retrieval by the mother (e.g. Allin &
417
Banks, 1972; Farrell & Alberts, 2002).
Vocalisations and communication
16
418
The second ultrasonic vocalisation is the ‘22 kHz long-call’, which occurs
419
mainly in aversive situations and might therefore indicate negative affect (Knutson et
420
al., 2002). Examples of such situations include social defeat (Van der Poel & Miczek,
421
1991), exposure to cat odour (Blanchard et al., 1991), administration of naloxone or
422
lithium chloride (Burgdorf et al., 2001), arthritic pain without analgesia (Calvino et
423
al., 1996), acute pain (Jourdan et al., 1995), acoustic startle (Kaltwasser, 1990) and
424
electric shocks (Kaltwasser, 1991). However, male rats make a similar vocalisation
425
after ejaculation (Van der Poel & Miczek, 1991), so this call might occur in two
426
subtly different forms, or might not reliably indicate negative affect.
427
The third ultrasonic vocalisation is the ‘50 kHz chirp’, which is apparently
428
associated with positive events (Knutson et al., 2002), and has even been suggested as
429
a form of laughter (Panksepp & Burgdorf, 2000). It occurs in anticipation of positive
430
social contact (Knutson et al., 1998; Brudzynski & Pniak, 2002), rewarding ‘tickling’
431
by humans (Panksepp & Burgdorf, 2000; Burgdorf & Panksepp, 2001; Panksepp,
432
2006), amphetamine or morphine administration (Knutson et al., 1999), and feeding
433
or rewarding electrical stimulation of the brain (Burgdorf et al., 2000), and also during
434
play (Knutson et al., 1998; Brudzynski & Pniak, 2002; Burn, 2006). However, again,
435
this vocalisation does not reliably indicate positive affect because it occurs in some
436
aversive situations, e.g. during morphine withdrawal (Vivian & Miczek, 1991),
437
aggression (Sales, 1972), and in certain painful situations (Hawkins et al., 2005).
438
Surprisingly little work has investigated the audible squeak. There may in fact
439
be several different types of squeak, because subjectively there is variation in the
440
quality of sounds produced (O. H. P. Burman, personal communication; personal
441
observation). Pups and their mothers make audible squeaks in the nest (e.g. Voipio,
442
1997), but this may be different from squeaking in other contexts. Squeaks occur
443
during nociception as they persist even when central nervous system analgesics are
444
given, which might suggest that they are detached from the emotional experience of
445
pain (Jourdan et al., 1995). They also occur during playing and fighting (Voipio, 17
446
1997; Burn et al., 2006a), and sometimes during handling, especially alongside
447
struggling behaviour (van Driel et al., 2004; Burn, 2006). They generally seem to
448
indicate negative affect, but do not necessarily occur alongside the 22 kHz long-call,
449
so there must be some qualitative or quantitative difference between the motivations
450
behind the two call types.
451
All of these vocalisations could have practical implications. Procedures or
452
environments that cause rats to vocalise could affect the behaviour and physiology of
453
all neighbouring rats within audible range. For example, playbacks of 22 kHz long-
454
calls caused freezing and decreased activity (Sales, 1991; Brudzynski & Chiu, 1995)
455
and increased latencies to emerge into an arena (Burman et al., 2007). Playbacks of
456
audible squeaks also caused conspecifics to orientate towards the speaker and
457
occasionally to squeak themselves (Voipio, 1997).
458
3.3
459
An awareness that rats can hear our voices is important, because of affects on
460
experimental results and rat welfare. Rats can hear and discriminate many elements of
461
the human voice (e.g. Pons, 2006), and pet rats can learn to respond to verbal
462
commands (e.g. Fox, 1997). In fact, rats can distinguish between some languages
463
(Toro et al., 2003), so the pitches, rhythms and accents of different human workers
464
could be at least partly responsible for rats being able to distinguish between
465
individual humans (McCall et al., 1969; Morlock et al., 1971; Davis et al., 1997; van
466
Driel & Talling, 2005). Shouting causes stress responses in farm animals
467
(Hemsworth, 2003), so this may also be true for laboratory rats, especially because
468
when humans speak with more emotional content, the higher-pitched and ultrasonic
469
content of our speech increases (Mason, 1969).
470
3.4
471
By default, most standard recording devices and speakers include no ultrasound, so
472
specialised equipment is necessary, such as ‘tweeter’ speakers and ultrasonic
Perception of the human voice
Sound recordings and playbacks
18
473
microphones (Björk et al., 2000). White noise, although aversive to rats (Voipio,
474
1997), is commonly used to standardise background noise in experiments, but
475
different speakers differ in their ultrasonic output, so comparisons across studies
476
might sometimes be invalid. Even a study that specifically investigated how
477
background noise affected rat behaviour in a maze, neither mentioned their ultrasonic
478
hearing abilities, nor used specialist equipment to produce the experimental white
479
noise (Prior, 2006), indicating that awareness of these auditory issues may be lacking
480
in some fields.
481
3.5
Echolocation There has been some debate about whether rats can echolocate (e.g. Rosenzweig
482 483
et al., 1955; Riley & Rosenzweig, 1957; Kaltwasser & Schnitzler, 1981; Forsman &
484
Malmquist, 1988). Blind rats can use self-generated sounds, reflected off solid
485
objects, to guide them in mazes (Rosenzweig et al., 1955; Riley & Rosenzweig,
486
1957). Also, sighted rats in darkness can discriminate between shelves close enough
487
to jump to and those too far away, but not if they are deafened (Chase, 1980). Some
488
studies described quiet ultrasonic ‘clicks’ (Chase, 1980; Graver et al., 2004), which
489
were produced more in darkness than in light, more before rats jumped to the platform
490
than after, and the decision to jump was faster in rats that clicked more (Graver et al.,
491
2004). However, rats seem not to have anything like the specialised echolocation
492
abilities of mammals such as bats or cetaceans. Indeed, some blind and blindfolded
493
humans can ‘echolocate’ using reflected sound, similar to rats (in Riley &
494
Rosenzweig, 1957), but there is no evidence that either species can use sound to build
495
up a detailed picture of their environment, as bats or cetaceans can.
496
4
497
Rats rely heavily on olfaction (e.g. Doty, 1986). They can quickly associate olfactory
498
cues with food rewards (Le Magnen, 1999a; Birrell & Brown, 2000), with this ability
499
even making them a suitable alternative to ‘sniffer’ dogs for locating contraband
Olfaction
19
500
substances (Otto et al., 2002). Rats can locate the direction of odorants, without
501
moving their heads, three orders of magnitude more quickly than we can (Rajan et al.,
502
2006). It is sometimes stated that albinism dampens olfaction, because albinos show
503
weaker avoidance of garlic than pigmented rats do (Keeler, 1942), but of course they
504
might simply be less averse to the scent. Humans are unusual mammals because a much smaller proportion of our
505 506
genome is devoted to olfaction, than other species (Gilad et al., 2003; Emes et al.,
507
2004; Rat Genome Sequencing Project Consortium, 2004; Quignon et al., 2005), and
508
our vomeronasal organ is vestigial or non-existent (e.g. Brennan & Keverne, 2004). In
509
contrast, rats not only possess main olfactory epithelia, but also well-developed
510
vomeronasal organs. Although the two systems overlap (reviewed in Shepherd, 2006),
511
the vomeronasal organ seems specialised for instinctive recognition of pheromones
512
and evolutionarily relevant compounds (Dulac, 1997; Holy et al., 2000; Brennan &
513
Keverne, 2004), while the olfactory epithelium is specialised for learned associations
514
between volatile scents and their implications (Dulac, 1997). The vomeronasal system
515
detects relatively non-volatile compounds, requiring the rat to lick or imbibe some
516
compounds before it can detect them (Brennan & Keverne, 2004). Here ‘olfaction’
517
includes both systems, because in most cases the specific odorant or detection
518
mechanism is currently unknown. The focus is on olfactory communication, but some
519
significant scents within laboratory environments are also discussed.
520
4.1
521
Rat olfactory communication is well-developed, yet remains little understood by
522
humans. Much communication is mediated through urine, but rats have many scent
523
glands, including the sebaceous, preputial, clitoral, perineal, salivary, anal, plantar,
524
and Harderian glands. Through scent, rats can gain information about each others’
525
gender (Alberts & Galef, 1973; Moore, 1985; Brown, 1992; Garcia-Brull et al., 1993),
526
reproductive state (Gawienowski et al., 1975; Manzo et al., 2002; Zala et al., 2004),
Overview of rat olfactory communication
20
527
genetic relatedness (Wills, 1983; Hurst et al., 2005), dominance (Krames et al., 1969),
528
health status (Zala et al., 2004), and individual identity (Hopp et al., 1985; Gheusi et
529
al., 1997). Rats also recognise familiar conspecifics using olfaction (Burman &
530
Mendl, 2003), not through a shared ‘colony scent’, but through remembering
531
individual odours (Alberts & Galef, 1973; Carr et al., 1976). These odours can be
532
determined genetically or be acquired from the environment (Schellinck et al., 1991;
533
Schellinck & Brown, 2000; Hurst et al., 2005). Laboratory rats may not be completely isolated from conspecifics even when
534 535
individually housed, because scents from neighbouring cages, or experimental
536
apparatus and instruments can influence them (unless they are in individually
537
ventilated cages). These scents can profoundly affect rats, as described below,
538
although it should be mentioned that isolation itself also affects these social animals
539
(e.g. Day et al., 1982; Hurst et al., 1997; Sharp et al., 2002; Westenbroek et al., 2005).
540
4.2
541
Much sexual behaviour in rodents is olfactorily mediated. The ‘Bruce effect’,
542
whereby female mice abort their offspring upon encountering the volatile scent of
543
unfamiliar males (Bruce & Parrott, 1960), seems not to occur in rats. However, the
544
‘Whitten effect’, in which volatile male scents trigger oestrus in females (Whitten,
545
1959), and the ‘Lee–Boot effect’, when females housed without males show
546
suppressed, irregular oestrus cycles (Van Der Lee & Boot, 1956) do occur relatively
547
weakly in rats. In rats and mice, male odour accelerates the onset of puberty in
548
females, in a phenomenon labelled the ‘Vandenbergh effect’ (Vandenbergh, 1969,
549
1976).
550
Scent and reproduction
The scent of female rats, especially those in oestrus, stimulates male sexual
551
behaviour, but also urinary-marking (Manzo et al., 2002) and competitive aggression
552
(Alberts & Galef, 1973). It is possible therefore, that housing males where they can
553
smell females could affect their physiology and behaviour, affecting research, and 21
554
might affect their welfare either way. The vomeronasal system, probably responsible
555
for detecting these scents, habituates to stimuli less easily than most sensory systems
556
(Holy et al., 2000), so the effects might be persistent. However, since the vomeronasal
557
organ requires direct physical contact to detect some pheromones (Brennan &
558
Keverne, 2004), the problem might only exist if the scent is volatile. Other important scents here include those mediating the mother–pup
559 560
relationship. For example, diodecyl proprionate, a pup preputial gland pheromone,
561
induces maternal licking (Brouettelahlou et al., 1991). Mother rats produce various
562
odours aiding pup survival, including those guiding pups to the nipples, and those
563
deposited in the bedding that reduce pup activity, keeping them in the nest (Porter &
564
Winberg, 1999). Also, pregnant females release a non-volatile pheromone that
565
prevents infanticide by cohabiting males (Mennella & Moltz, 1988). Perhaps it is the
566
removal of these scents that increases the likelihood of pups being cannibalised when
567
rats’ cages are cleaned within the first few days of birth (Burn & Mason, in press).
568
4.3
569
Aggression in male rodents can be triggered by novel (usually male) scents, so rats
570
rendered anosmic show little aggression in resident–intruder tests (Alberts & Galef,
571
1973). Habituation to familiar or self-scents plays a large role in reducing aggression
572
between familiar or related individuals. For example, aggression is reduced between
573
more familiar individuals (Alberts & Galef, 1973; Garcia-Brull et al., 1993) and
574
between more closely related individuals (Nevison et al., 2003). Some inbred mouse
575
strains cannot discriminate between familiar and unfamiliar conspecific odours,
576
resulting in reduced aggression (Nevison et al., 2003). This could also be true for rats.
577
In fact, unfamiliar male scents not only stimulate aggression, but also defensive
578
behaviour in subordinate males encountering dominant male odours. Rats defeated by
579
an alpha-male, subsequently show avoidance and fear behaviour upon encountering
580
the scent of other alpha-males (Williams & Groux, 1993; Williams, 1999).
Olfactory modulation of aggression
22
581
This said, while cage-cleaning – which removes scent marks – provokes
582
aggression in male mice (Gray & Hurst, 1995; Van Loo et al., 2000), in familiar rats it
583
merely provokes non-aggressive skirmishing (Burn et al., 2006a; Burn et al., 2006b);
584
perhaps for this reason cage-cleaning frequency seemingly has no long-term effects
585
on male rat welfare.
586
When unfamiliar rats are to be housed together, exposing them to each other’s
587
scents for a few days before allowing physical contact may prevent aggression (e.g.
588
Bulla, 1999). Alternatively, aggression can sometimes be prevented by masking
589
unfamiliar conspecifics using another unfamiliar, neutral scent. In rats evidence is
590
anecdotal, but in a controlled study of mice, chocolate or sheep’s wool odours reduced
591
resident–intruder aggression (Kemble et al., 1995).
592
Finally, it is worth mentioning that odour-mediated aggression does not only
593
occur between males. For example, mother rats able to smell their own pups show
594
aggression towards intruders – neither visual, tactile, nor auditory cues from the pups
595
elicit this aggression (Ferreira & Hansen, 1986).
596
4.4
597
Rats are generally attracted to areas smelling of conspecifics (e.g. Galef & Heiber,
598
1976; Mackay-Sim & Laing, 1980), but scents released during negative or positive
599
experiences, can make those areas aversive or more attractive, respectively.
600
Communication about experiences
Rats produce ‘alarm’ odour when they experience electric shocks (Mackay-Sim
601
& Laing, 1980; Abel & Bilitzke, 1990; Williams & Groux, 1993; Kiyokawa et al.,
602
2004), transport between rooms (Beynen, 1992), and the events and disturbances
603
accompanying carbon dioxide euthanasia (Ware & Mason, 2003). They probably also
604
produce it in forced-swim tests (Abel & Bilitzke, 1990), but no unstressed controls
605
were used so rats may simply have been responding to odours left by an unfamiliar
606
male. Alarm odour is more powerful with more severe stressors (Mackay-Sim &
607
Laing, 1980). The molecule(s) involved have not yet been identified, but a candidate 23
608
is 2-heptanone; more of this is present in urine from stressed rats, but diazepam during
609
the stressor does not reduce the amount produced (Gutiérrez-García et al., 2006).
610
In recipients, alarm odour increases freezing behaviour (Williams, 1999;
611
Kikusui et al., 2001), activity (Mackay-Sim & Laing, 1980; Abel & Bilitzke, 1990;
612
Kikusui et al., 2001; Ware & Mason, 2003), body temperature (Kikusui et al., 2001),
613
hypothalamic–pituitary–adrenal activity (Takahashi et al., 1990; but see Mackay-Sim
614
& Laing, 1980), urination (Stevens & Koster, 1972), and latency to approach rewards
615
(Mackay-Sim & Laing, 1981; Ware & Mason, 2003). It also causes avoidance
616
compared with the scent of unstressed conspecifics (Mackay-Sim & Laing, 1980).
617
Experience can affect responses to alarm odour, with rats avoiding the odour of
618
shocked rats more if they have experienced shock themselves, but not necessarily if
619
they have experienced defeat by an alpha-male (Williams & Groux, 1993).
620
A somewhat separate body of literature describes ‘frustration’ or ‘non-reward’
621
odour, produced when anticipated rewards are withheld (Collerain & Ludvigson,
622
1972; Ludvigson et al., 1985; Taylor & Ludvigson, 1987). Again this odour causes
623
avoidance, but unlike alarm odour, no fear responses to it have been reported. It seems
624
not to exist in urine (Collerain & Ludvigson, 1972), unlike alarm odour (Mackay-Sim
625
& Laing, 1981), but both are also produced from other bodily sources yet to be
626
identified (Mackay-Sim & Laing, 1981; Weaver et al., 1982).
627
Rats probably also produce a ‘reward’ odour, although this has mainly been
628
tested against non-reward situations (i.e. frustration odour), with no neutral rat odour
629
control. Nevertheless, a rat’s trail is more attractive if laid down after the rat receives
630
a reward than before (Galef & Buckley, 1996), and when it perceives a signal that
631
reliably predicts reward (Ludvigson et al., 1985). However, the attraction of rats to
632
reward odour is much weaker than the avoidance of frustration odour, when compared
633
against the same ‘no odour’ control (Taylor & Ludvigson, 1980).
24
634
The release of alarm odour means that rat welfare and experimental aims might
635
be compromised if neighbouring conspecifics are distressed by illness, injury, or
636
experimental procedures (Beynen, 1992). Any of these odours can bias rats’ decisions
637
in choice tests (Collerain & Ludvigson, 1972; Aoyama & Okaichi, 1994; Mitchell et
638
al., 1999), increase ‘baseline’ stress in subsequently tested rats or supposed control
639
ones (Beynen, 1992; Kikusui et al., 2001), and alter behaviour in tests such as swim
640
tests (Abel & Bilitzke, 1990), and open field or novelty tests (Mackay-Sim & Laing,
641
1981; Takahashi et al., 1990; Ware & Mason, 2003). There has apparently been no evaluation of effective ways to clean experimental
642 643
apparatus; various cleaning agents are used, which probably vary in efficacy and may
644
have intrinsic odours that affect rats. Alcohol is commonly used, but in pigs, its
645
volatile components can reduce cortisol levels in open field tests (Thodberg et al.,
646
2006).
647
4.5
648
Rats can learn about specific foods from conspecific odours. Carbon disulphide,
649
present in rats’ breath (Galef et al., 1988), causes rats to strongly prefer novel foods
650
eaten by their cagemates versus other novel foods (e.g. Strupp & Levitsky, 1984). The
651
preferences can persist for at least 30 days, even without opportunity to sample the
652
foods during that time (Galef & Whiskin, 2003b).
653
Communication about food
Aversion to novel foods can be caused by the ‘poisoned partner effect’ (Lavin et
654
al., 1980). Here if a novel food is eaten by a rat, which then encounters the odour of a
655
poisoned conspecific, the healthy rat will subsequently avoid the novel food, even if
656
the poisoned rat did not eat it (Stierhoff & Lavin, 1982). Strangely, the healthy rat
657
only avoids food that it itself has eaten, rather than that eaten by the poisoned rat, and
658
therefore not necessarily the poisonous food (Galef et al., 1990). In fact, exactly as
659
described above, the healthy rat actually prefers novel foods after smelling them on
660
the poisoned rat’s breath (Galef et al., 1990). 25
661
Lactating rats also avoid novel foods ingested just before their pups become ill,
662
because of an odour released by pups with gastrointestinal illness (Gemberling, 1984).
663
The odour causes no aversion in males or nulliparous females, and is not released by
664
pups stressed in other ways, so it seems more specific than the poisoned partner
665
effect.
666
4.6
667
Most of the scents relevant to laboratory rats are those within the cage itself. Apart
668
from those produced by conspecifics or food, others could include detergent residues,
669
bedding materials, and microbial products from the breakdown of food or excreta.
670
Cage-cleaning abruptly changes the olfactory environment, which might contribute to
671
post-cleaning changes in rat behaviour and physiology (Burn et al., 2006a). Also, like
672
gerbils, rats might more accurately discriminate scents in a test arena on days when
673
their cages are clean rather than soiled (Dagg et al., 1971).
Scents in the laboratory
674
Another salient source of smell for laboratory rodents might be their human
675
handlers. Rats respond differently towards different humans (McCall et al., 1969;
676
Morlock et al., 1971; Davis et al., 1997; van Driel & Talling, 2005), mostly because
677
of differences in odour (McCall et al., 1969). People smell different due to genetic
678
factors and environmental ones, such as diet, smoking, perfume, soap, and deodorant.
679
Regular rodent handlers may also be ‘marked’ with odours from previously handled
680
rodents, sometimes including reward or alarm odours.
681
Additionally, rats might fear humans carrying scents from their pets, especially
682
if the pet is a predatory species. Rats innately fear predator odours, including cats and
683
mustelids (reviewed in Blanchard et al., 2003), but apparently not dogs. Rats cannot
684
easily habituate to predator odours (Blanchard et al., 1998), showing increased
685
corticosterone, freezing and vigilance, elevated plus-maze anxiety and endogenous
686
opioid analgesia, and suppressed electric-prod burying, and impaired working
687
memory (Williams, 1999; Blanchard et al., 2003). Predator odours also elicit fear26
688
related fast-waves and reduce cell-proliferation in the dentate gyrus (Heale et al.,
689
1994; Tanapat et al., 2001).
690
It is even possible that rats would instinctively fear human odour – wild rats
691
usually avoid close human contact, and any such fear of humans might have escaped
692
our notice, of course, it would require a controlled experiment not involving human
693
presence.
694
Many odours from synthetic products used in laboratories could affect rodents.
695
While several reviews compare the efficacy of detergents for cleaning animal cages
696
(e.g. Heuschele, 1995), none discuss their potential olfactory impacts on the animals.
697
Yet, some organic solvents (e.g. xylene, toluene, diethyl ether, and methyl
698
methacrylate) cause avoidance and fast-waves in the dentate gyrus, just as predator
699
odours do (Heale et al., 1994). These solvents constitute many everyday substances,
700
including some inks, glues, and paints; indeed, identification-marking rodents with
701
inks or dyes can affect their anxiety profiles (Burn et al., in press) and cause them to
702
become submissive to unmarked cagemates (Lacey et al., 2007).
703
Many odorants that smell subjectively pleasant to humans, often therefore being
704
present in perfumed products or human diets, can also influence hypothalamo-
705
pituitary-adrenal activity and immune responsiveness, positively or negatively
706
(Komori et al., 2003). Rose oil (de Almeida et al., 2004) and ‘green odour’, trans-2-
707
hexenal (Nakashima et al., 2004), are anxiolytic to rats. Citrus oils are analgesic
708
(Aloisi et al., 2002), but can have complex effects on rodent anxiety (Komori et al.,
709
2003; Ceccarelli et al., 2004). In rat pups, peppermint increases mortality and
710
decreases activity (Pappas et al., 1982), and rats avoid the scent of garlic (Keeler,
711
1942) and rosemary (R. M. J. Deacon, personal communication). Many of these
712
effects could inadvertently introduce variation between experiments, but some could
713
be used as non-nutritive environmental enrichments or rewards. Also, anxiolytic
27
714
scents could be easily administered to rats in mildly stressful situations (de Almeida et
715
al., 2004; Nakashima et al., 2004).
716
5
717
Like us, rats are opportunistic omnivores; their ecological niche is characterised by
718
sampling diverse food substances and remembering their nutritional consequences
719
(e.g. Capaldi, 1996). They rapidly learn aversions to harmful novel foods, which can
720
be a problem in pest control situations when they ingest sub-lethal quantities of bait.
721
Rats, particularly wild strains, are neophobic, being reluctant to consume novel food
722
(Galef & Whiskin, 2003a). They initially sample only small amounts of novel food (if
723
any at all), but if it proves safe, they later readily consume it, often in preference to
724
more familiar foods (Calhoun, 1963). Under natural conditions, this cautious but
725
explorative behaviour might help them obtain a full nutritional complement, reducing
726
reliance on any one food type, while avoiding poisoning.
727
Gustation
Rats detect similar taste dimensions to humans, i.e. sweetness (carbohydrates
728
and artificial sweeteners), saltiness (sodium salts), sourness (hydrogen ions),
729
bitterness (quinine, caffeine, most natural toxins, and some others) (Grill & Norgren,
730
1978), and umami (amino acids, such as glutamate) (e.g. Smith & Margolskee, 2001).
731
As with humans, sweetness and umami are rewarding, bitterness is usually aversive,
732
and saltiness and sourness are only pleasant at low concentrations (Grill & Norgren,
733
1978; Berridge, 2000). They also initially strongly avoid capsaicin, the ‘hot’ taste of
734
chilli, but often consume it readily once it becomes familiar (Jensen et al., 2003).
735
However, rats do not perceive certain artificial sweeteners as being ‘sweet’ (Sclafani
736
& Abrams, 1986; Dess, 1993; Sclafani & Clare, 2004), and they may have separate
737
receptors for sugars and starch (Sclafani, 1987). Their bitterness thresholds for some
738
compounds differ from ours (Glendinning, 1994; Mueller et al., 2005), allowing
739
denatonium benzoate – which tastes less bitter to rats than to humans and some other
740
animals – to be added to baits to prevent its consumption by non-target species 28
741
(Hansen et al., 1993). There are also some strain and sex differences in rat gustation
742
(Boakes et al., 2000; Clarke et al., 2001).
743
In fact, ‘flavour’ involves not only gustation, but also olfaction and tactile
744
sensations (Smith & Margolskee, 2001). For completeness, these senses are not
745
separated here when discussing the practical implications of rat gustatory biases.
746
5.1
747
Laboratory rodents usually have no opportunity to sample different foods, typically
748
being fed a palatable, dry, nutritionally complete diet, in powder form or as pellets.
749
These diets are easily stored, inexpensive, and require little preparation (Lane-Petter,
750
1975), and they aid standardisation between experiments. Laboratory rats will also
751
taste their mothers’ milk, bodily secretions from themselves or conspecifics (if
752
socially housed), their cage surfaces, and perhaps human hands or gloves, and
753
bedding material (if provided). Hence, scope for learning taste–nutrient associations is
754
very limited, rendering the gustatory sense largely redundant in laboratories.
755
Taste in the laboratory
For other sensory modalities, sensory deprivation reduces the volume and
756
functioning of the associated brain regions. For example, the visual cortices of rats
757
reared in darkness are permanently underdeveloped (Fagiolini et al., 1994), while
758
sensory deprivation only temporarily limits olfactory bulb (Cummings et al., 1997)
759
and barrel cortex development (Polley et al., 2004; but see Rema et al., 2003).
760
However, despite rats frequently being used as models in taste research, precisely
761
because their gustatory perception is supposedly similar to ours, the effects of
762
gustatory deprivation on the brain and behaviour are apparently unknown. The effects
763
may be minimal if taste is tightly genetically controlled, but alternatively, lack of
764
gustatory experience could, for example, exaggerate rats’ neophobia or diminish their
765
gustatory learning abilities.
29
766
5.2
767
It is unclear whether rats can appropriately self-regulate their nutritional intake, given
768
the opportunity. Most discrepancies between findings are probably due to differences
769
between the diets offered to rats (Naim et al., 1985; Sclafani, 1987; Prats et al., 1989),
770
and circadian variations in intake patterns (Larue-Achagiotis et al., 1992). Rats
771
generally do select foods appropriate for their changing nutritional needs, but like
772
humans, they are biased towards sugary or fatty foods. They are consequently also
773
prone to obesity if offered palatable, calorific diets (Naim et al., 1985; Sclafani, 1987;
774
Prats et al., 1989).
775
Nutritional regulation
Because laboratory rodent diets are homogenous, they allow no qualitative
776
nutritional regulation. Generally, this is unproblematic because the diets have
777
sustained rodent populations for many decades, without apparent negative effects on
778
breeding, health, or longevity. However, although special formulations are available,
779
many widely used diets cover all age and sex categories: oestrus females, weanling
780
pups, and elderly males alike. Moreover, they are often common to rats and mice.
781
Thus, within this diversity, individuals might sometimes have different nutritional
782
requirements from that provided. In standardising diets to this extent, we might
783
inadvertently increase, rather than decrease, variation in rodents’ internal nutritional
784
states because they have no opportunity to regulate them.
785
Some dietary supplements can enhance laboratory rat health, calling into
786
question the completeness of homogenous diets. For example, blueberries, high in
787
antioxidants, prevent cognitive deficits in aging rats (Casadesus et al., 2004), and as
788
mentioned previously, other dietary supplements prevent retinal damage (Li et al.,
789
1985). Also, in hamsters, supplementation with seeds and rabbit chow increased pup
790
growth, and reduced cannibalism by the mothers (Day et al., 2002).
30
791
5.3
Refinement within the homecage
792
Palatable diets may provide rats with ‘enjoyment’ (Lane-Petter, 1975) or hedonic
793
experiences, with palatable and unpalatable foods eliciting distinctive behavioural
794
expressions that are homologous to human gustatory expressions (Berridge, 2000).
795
Most welfare efforts concentrate on reducing negative welfare, but facilitating
796
positive welfare, such as pleasure from food or foraging, should not be neglected (e.g.
797
Balcombe, 2005). Food-related environmental enrichments might be particularly
798
relevant for generalists, like rats, because their natural ecology incorporates diverse
799
food types, varying through time and space. However, the idea of food-related
800
enrichment has been little explored for laboratory rats, and yet it could improve their
801
welfare (Johnson & Patterson Kane, 2003), provided obesity is avoided (e.g. Mattson,
802
2005). There are three main aspects of food that could be varied for enrichment
803
purposes: nutritional content, flavour, and physical presentation.
804
5.3.1
805
Providing rodents with very nutritionally diverse diets may be undesirable for
806
practical reasons (Lane-Petter, 1975; Key, 2004), and because they encourage obesity
807
(Mattson, 2005), and may increase variation. Nevertheless, offering some opportunity
808
to nutritionally self-regulate could be beneficial, as suggested above. In some animal
809
facilities, seeds and nuts are scattered onto rats’ bedding; rats become very active
810
upon hearing them being scattered in neighbouring cages, and continue foraging for
811
many hours (Key, 2004). Since the seeds would constitute only a very small
812
proportion of the diet, they are unlikely to impact heavily on nutritional regulation,
813
but could allow some relevant gustatory stimulation and regular hedonic experiences.
814
Proper evaluation of the effects is necessary however; the most relevant study so far
815
seems to be one, mentioned earlier, when seed supplements enhanced hamster pup
816
growth and decreased cannibalism (Day et al., 2002).
Nutritional content
31
817
5.3.2
818
Even without nutritional value, gustatory enrichment could be achieved; providing
819
daily non-nutritional pina-colada flavour treats to breeding mice increased the number
820
of pups weaned (Inglis et al., 2004), suggesting that the hedonistic aspects alone of
821
scatter-feeding are beneficial.
822
Flavour
Domesticated rats value variety, and will substitute a preferred food that has
823
been their sole diet for several days for a less preferred, newly available food (Galef
824
& Whiskin, 2003a, 2005). They also consume more food if provided as a succession
825
of varied ‘meals’ rather than homogenous meals (Treit et al., 1983; Clifton et al.,
826
1987; Le Magnen, 1999b). These preferences exist even when foods differ primarily
827
in flavour not nutritional value, such as when cinnamon, cocoa, ‘all spice’, or
828
marjoram are added to normal chow (as in the above five studies). These additives
829
presumably have negligible bioactivity, being common non-nutritive components of
830
human diets, but confirmation in rats is required. The above studies suggest that
831
obesity might be a risk because of the increased food consumption, but they were all
832
relatively short-term, so rats might down-regulate their intake of variable food over
833
time. Le Magnen (1999b) found that if ‘variable days’ were alternated with
834
‘homogenous days’, rats ate less food than normal on homogenous days, perhaps
835
compensating for over-eating on variable days.
836
5.3.3
837
Finally, enrichment might be achieved through varying dietary presentation. Soft ‘wet
838
mash’ (chow soaked in water) is often used to help sick or weak rats gain weight, and
839
usually any healthy cage-mates also prefer the mash to freely available pellets.
840
However, it is an impractical enrichment for healthy rats, being messy and
841
encouraging microbial growth (Lane-Petter, 1975). Occasionally scattering chow
842
pellets within the cage allows rats to eat in their natural posture, holding the pellet in
Physical presentation
32
843
their forepaws (Bruce, 1965), and they more readily consume these pellets than those
844
in the hopper (personal observation). Captive rats also ‘contra-freeload’, choosing food that requires handling and
845 846
preparation, even when prepared food is available (Carder & Berkowitz, 1970). This
847
may be because most of a wild rat’s time and effort would be devoted to foraging
848
(Johnson & Patterson Kane, 2003). Scattering small food items, such as the
849
aforementioned seed mixes or chow pellets, in bedding allows rats to forage, which
850
may be rewarding in itself. Scatter-feeding rarely triggers competitive aggression
851
because the food is spatially distributed. Commercially available rodent puzzle-
852
feeders are also available, although they are uncommon in laboratories and are not
853
always easily sourced.
854
5.4
855
The generalist feeding habits of rats can be exploited in research, improving
856
experiments ethically, enhancing rats’ cooperation, and reducing interference from
857
stress. Drugs and inoculants are often delivered by gavage, a tube inserted via the
858
mouth into the stomach, which can be technically difficult, and causes stress,
859
respiratory distress, and occasionally even death (Balcombe et al., 2004). However,
860
substances can be successfully delivered within palatable vehicles that rats will
861
voluntarily consume, provided there is no interference with the active ingredient.
862
Fruit- or beef-flavoured gelatine is commonly used but some rats only reluctantly
863
consume it, so it can be worth trying several alternatives (Hawkins et al., 2004).
864
Another example is to use small amounts of chocolate (Huang-Brown & Guhad,
865
2002). Taste aversion can develop if the vehicle becomes associated with illness, but
866
giving rats prior experience with the unadulterated food can prevent this. Some
867
substances can also be microencapsulated and added to chow for long-term studies
868
(Melnick et al., 1987; Dieter et al., 1993; Yuan et al., 1993).
Refinement of experiments
33
869
Preferred rewards can often be used to motivate rats to perform tasks in
870
experiments, rather than using punishments or prior deprivation. Deprivation is a
871
powerful motivator, but can undesirably affect behaviour, physiology,
872
neurochemistry, and drug efficacy (Slawecki & Roth, 2005). Moreover, it is
873
sometimes unnecessary, because undeprived rats will often work – albeit to a limited
874
extent – for preferred rewards, including commercially available reward pellets,
875
sucrose solution (Slawecki & Roth, 2005), or breakfast cereals (e.g. Ellis, 1984). Prats
876
and colleagues (1989) found that rats did not readily consume cheese, chocolate or
877
fruit-candy, and instead preferred other foods offered, including banana, cookies,
878
standard chow pellets, and liver pâté. Large quantities of dairy products (DiBattista,
879
1990) and chocolate (Huang-Brown & Guhad, 2002) should be avoided as they harm
880
rodent health. Undeprived rats are particularly motivated to earn rewards if
881
experiments coincide with their active period (Hyman & Rawson, 2001), with a
882
shifted light cycle enabling practical working hours (see the section on Vision).
883
Neophobia can be eliminated by providing the palatable incentive in the homecages of
884
rats several days before experiments.
885
Finally, food must often be withheld overnight before surgery or intraperitoneal
886
injections. This deprivation causes weight loss, and reduced hepatic weight and blood
887
glucose, and potentially, emotional distress from hunger. However, providing sugar
888
cubes to the rats can prevent these problems, while gastrointestinal volume is still
889
reduced, as required (Levine & Saltzman, 1998).
890
6
891
Rat somatosensation could be considered from many different angles. Here, the focus
892
is on that relating to the ability of rats to explore and interact with their environments.
893
In the rat somatosensory cortex, the vibrissae (sensory whiskers), nose and mouth,
894
forepaws, and sinus hairs on its wrists, are particularly well-represented. In fact, the
895
forepaws are represented twice each, and the whiskers and sinus hairs have
Somatosensation
34
896
specialised granular aggregates devoted to them (Hermer-Vazquez et al., 2005). In
897
general, rat and human somatosensation seem similar, but there are two main
898
differences that noticeably affect rat behaviour. Firstly, rats’ vibrissae are extremely
899
sensitive (Arabzadeh et al., 2005), being comparable to primate fingertips (Carvell &
900
Simons, 1990). Rats can whisk them independently of each other across surfaces to
901
make fine tactile discriminations (Guic-Robles et al., 1989; Carvell & Simons, 1990).
902
In a study investigating rats’ numerical competencies, subjects could not discriminate
903
between two, three or four tactile stimuli delivered to the body, but they succeeded
904
when the stimuli were delivered to a single vibrissal hair (Davis et al., 1989). The
905
vibrissae also detect differences in mechanical resonant frequencies, with the shorter
906
anterior vibrissae detecting higher frequencies than the longer posterior ones
907
(Neimark et al., 2003).
908
The second obvious difference from humans relates to thigmotaxis; the bias of
909
rats towards maintaining physical contact with vertical surfaces. In fact, thigmotaxis
910
underlies many tests of ‘anxiety’ (Treit & Fundytus, 1988), because when rats
911
perceive environments as threatening, they stay closer to vertical surfaces, such as the
912
boundaries of open field arenas, or the closed arms of elevated plus-mazes. The
913
thigmotactic bias may not be strictly somatosensory, perhaps also incorporating visual
914
preferences for avoiding light exposure. Rats that lack vibrissae on one side prefer to
915
maintain wall-contact on their intact side, suggesting the vibrissae play a role (Meyer
916
& Meyer, 1992). The implications of rat somatosensation include the impact of environmental
917 918
enrichment on rat somatosensory development generally, and implications of the
919
vibrissal sense for experiments and housing.
920
6.1
921
Environmental enrichment profoundly affects the somatosensory and barrel cortices.
922
In rats kept in enriched rather than barren environments, the primary somatosensory
Environmental enrichment and somatosensation
35
923
cortex representing the forepaws becomes 1.5 times larger (Xerri et al., 1996; Coq &
924
Xerri, 1998, 2001). The barren cages in these studies contained bedding, exerting their
925
effect despite rats being able to dig with their forepaws, so the difference might be
926
even more pronounced in rats housed on wire floors. Environmental enrichment
927
seemingly does not enhance textural discrimination abilities, but it does increase the
928
rate of learning such discriminations (Bourgeon et al., 2004). Enrichment can also
929
counteract age-related declines in hind-paw representation in the somatosensory
930
cortex, which is otherwise associated with impaired walking in aged rats (Godde et
931
al., 2002). Finally, in naturalistic environments, the representation of each whisker in
932
the barrel cortex becomes dramatically more well-defined compared with standard
933
cages (Polley et al., 2004).
934
The above studies combined several enrichment types, including social
935
contact, foraging opportunities, structural features and novelty, so it is unclear what
936
relative contributions were made by each enrichment type. It is lack of tactile contact
937
with conspecifics that apparently leads to the self-biting and tail manipulation seen in
938
isolated rats (Day et al., 1982; Hurst et al., 1997).
939
6.2
940
The sensitivity of the vibrissal sense (Davis et al., 1989; Guic-Robles et al., 1989;
941
Carvell & Simons, 1990; Arabzadeh et al., 2005) is probably under exploited in
942
learning tasks, where less salient visual cues are currently more widely used
943
(Dymond, 1995; Dymond et al., 1996; Birrell & Brown, 2000). However, laboratory
944
rats can sometimes lack vibrissae for various reasons, including ‘barbering’, when
945
hairs and often whiskers are removed by conspecifics (Garner et al., 2004). This
946
occurs in rats, albeit to a much lesser extent than in mice (Bresnahan et al., 1983;
947
Wilson et al., 1995). Other rats may lack whiskers due to their strain; some nude
948
rodent strains have no whiskers at all (e.g. Sundberg et al., 2000), but most have short,
949
kinked whiskers, giving a limited sensory range (e.g. Festing et al., 1978; Moemeka et
Vibrissae and the laboratory environment
36
950
al., 1998). Nude strains also lack the sensitive guard hairs otherwise dispersed through
951
the coat, and which would convey proprioceptive information. Both vibrissal absence and barrel cortex impairment through lack of
952 953
environmental enrichment (as described above), could have practical consequences.
954
Rats lacking vibrissae show impaired orientation towards tactile stimuli, and –
955
provided they have environmental enrichment – compensate by orienting towards
956
visual stimuli more than controls (Symons & Tees, 1990). Whiskers also aid
957
swimming, enabling animals to keep their heads above water (Ahl, 1986; Meyer &
958
Meyer, 1992), and consequently, rats lacking vibrissal sensation can drown in water
959
mazes and swim tests (Hughes et al., 1978).
960
Finally, vibrissae are important in social interactions, with whiskerless rats
961
being unable to avoid bites to their faces during fighting (Blanchard et al., 1977a;
962
Blanchard et al., 1977b). Because aggression between familiar rats is uncommon
963
(Burn et al., 2006b), whiskerless rats need not be socially isolated, except in cases
964
where aggression is observed. However, whiskerless rats may be injured if introduced
965
to unfamiliar conspecifics, when fighting is more likely.
966
7
967
It is impossible for us to know what it is like to be a `rat` (Nagel, 1974), but
968
knowledge of their sensory biases allows us to imagine what it might be like, as a
969
human, to have those biases within a laboratory rat’s environment. This insight, while
970
imperfect, could help predict how rats might be affected by different situations,
971
improving our experimental design and their welfare. In summing up then, an overall
972
theoretical picture of a rat’s perception of the laboratory could be as follows.
973
Summary
The rat’s sensitive eyes, shunning the intense artificial light, provide it with a
974
hazy view in predominantly grey, ultra-violet and green hues. From within its cage, it
975
hears the chirps, squeaks and whines of its neighbours, gaining information that we 37
976
cannot hear unaided and are yet to understand. Background noise consists of the low
977
babbles and hisses of distinctively scented humans, and the unregulated drones and
978
blasts of ultrasonic sounds. Scents provide visceral warnings and enticements, induce
979
new motivations, and inform the rat about social possibilities outside the cage. The
980
environment wafts a succession of scents, from pleasant, calming fragrances to the
981
innately alarming odours of intangible predators. The rat tastes little apart from its
982
dry, satiating homogenous diet. Its vibrissae provide a protective, finely tuned force-
983
field to feel the details of the cage surfaces; with the rat perceiving security from close
984
contact with the solid walls.
985
8
986
Conclusion Knowledge of the sensory gulfs and similarities between ourselves and this
987
commonly used research animal can improve science and enhance rat welfare. More
988
work is still necessary to understand rat perception, and even more so for less well-
989
researched species. The aim of this review is to make current knowledge accessible to
990
researchers, rat caretakers and rodent specialists, in the hope that it will enable
991
tangible improvements in experimental design and rat welfare.
992
Acknowledgements
993
Many thanks to Georgia Mason for her detailed comments and encouragement,
994
and also to Robert Deacon, Mark Ungless, Jennifer Bizley, and Alex Weir for their
995
comments.
996
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997 998 999 1000 1001 1002 1003
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Figure 1
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Visual perception of rat strains in visual-based behavioral tasks, reprinted from
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Prusky and colleagues (2002) (with permission from Elsevier and the authors). The
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original image (top-left) has been blurred to model the perception of rats with acuities
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of 1.5 c/d (top-right; Fisher–Norway), 1.0 c/d (bottom-left; Dark Agouti, Long-Evans,
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wild) and 0.5 c/d (bottom-right; Fisher-344, Sprague–Dawley, Wistar) when the
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image subtends 10 degrees. This approximates the size of the image if it were used as
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a visual cue in a typical visuo-behavioural task (see Prusky et al., 2002 for details).
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