1. Genetic traits: Genetic variability among many animal species complicates our understanding of the effects of stress and distress in laboratory animals. Multiple studies in the mouse have shown that generalizations even across a single species can be problematic. Selective breeding has produced hundreds of inbred mouse strains, providing extensive genetic and phenotypic variability (Beck et al. 2000; Silver 1995). A mouse strain is classified as inbred after 20 inbreedings (that is, 20 generations of brother × sister or offspring × parent matings), at which point its members are virtually genetically identical because at the 20th or subsequent generations all animals are traceable to a single breeding pair. One cannot assume that mice from different inbred strains are alike (or even similar), perform identically, or experience and react uniformly to stimuli—stressful or otherwise. In fact, inbred strains of mice differ in almost every behavioral, sensory, motor, and physiological trait studied to date, such as anxiety, learning and memory, brain structure and size, visual acuity, acoustic startle, exploratory behavior, alcohol sensitivity, depression, pain sensitivity, and motor coordination (Crawley et al. 1997; for more references see Additional References). What is typical for one strain—for example, high levels of play behavior or social interaction (Moy et al. 2004) or novelty seeking and exploratory behavior (Bolivar et al. 2000; Kliethermes and Crabbe 2006)—may not be characteristic of another.

    For these reasons different inbred murine strains respond to stress differently and thus may well experience distress in different ways. Indeed, a number of behavioral studies provide evidence that strain differences in distress susceptibility are likely. For instance, inbred strains differ in performance on anxiety, depression, and fear learning assays (Balogh and Wehner 2003; for more references see Additional References). Correlating behavioral performance across such matrices can provide some indication of basic genetic differences among strains in response to stressful situations (Ducottet and Belzung 2005). When exposed to a month of unpredictable mild stress (e.g., cage tilting, damp bedding, lights on for a short period during the dark phase) most strains groom themselves less resulting in poor fur condition, while only a few display heightened aggression levels (Mineur et al. 2003). In general, inbred strain differences appear in the stress-induced hyperthermia model (Bouwknecht and Paylor 2002; van Bogaert et al. 2006) and in stress-invoked autonomic responses (body temperature and heart rate), although the latter are also a function of the intensity of the insult applied (van Bogaert et al. 2006). Behavioral differences have also been observed in primates. High reactor monkeys1 are much less likely

1

It is now well established that there are marked individual differences in reactivity among nonhuman primates when animals are exposed to novel situations or to relatively minor changes in their social or physical environment. Some rhesus monkeys (~20%) respond to



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