At Flinders University in Australia, two other lines of rats were developed in the late 1970s (Overstreet et al. 1979) by selective breeding for differences in the hypothermic response to the cholinesterase inhibitor diisopropylfluo-rophosphate. This approach aimed at reversing the order of questions asked by typical selective breeding programs; it chose a physiological response to specific pharmacological agents as the selection criterion. Only afterwards did behavioral alterations enter the evaluation in order to identify possible anxiety-related or depressive-like characteristics. From a number of various findings it was concluded that the Flinders sensitive line, being hypersensitive to cholinergic agonists, may rather represent an animal model of depression more than anxiety disorder, because these rats exhibit several symptom patterns of depression, such as reduced locomotor activity, reduced body weight, increased rapid eye movement (REM) sleep, and cognitive (learning) deficits (Overstreet 1993). However, evidence that cholinergic hypersensitivity might be the leading cause of depression is limited, and this hypothesis is further to be questioned by the therapeutic efficacy of new antidepressants lacking anticholinergic properties. Notably, Flinders sensitive line rats show exaggerated immobility in the forced swim test (see Sect. 2.2.4) and this behavior returns to normal after treatment with antidepressants, including those without anticholinergic effects (Overstreet et al. 1995). This in turn is of interest in connection with recently reported changes in serotonergic activity in these animals (Zangen et al. 1997).
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