Center investigators are studying numerous genes and their protein products in the brain's reward circuits todefine their role in the regulation of mood and motivation under normal circumstances and in animal modelsof depression and antidepressant action. To accomplish this goal, the Behavioral Core has established anextremely broad battery of behavioral tests in rats and mice. This battery includes routine measures oflocomotor activity and anxiety-like behavior,, as well as several standard depression-related tests such as theforced swim and learned helplessness tests. The battery also incorporates several additional assays thatprovide complementary information about an animal's affective state; these include measures of sexualbehavior, incentive motivation for food, intracranial self-stimulation, social interaction, and sophisticatedcognitive tasks, to name some examples. In addition, Core personnel continually work to extend this batteryto additional tests. For example, we recently adapted the social defeat paradigm, where certain behavioralabnormalities respond to chronic (but not acute) antidepressant treatment, to study stress-inducedneuroadaptations in mouse brain. The imperative to employ such a large battery of behavioral tests is that itis difficult to infer something about complex behavior from a single test or even a limited number of tests.Rather, by utilizing numerous complementary measures we are able to infer, with much greater accuracy,the role of a given gene in complex behavior related to depression. By consolidating these behavioral testswithin a centralized Core, we can ensure rigorous control over the data as well as facilitate comparisons andcontrasts of experimental results from the individual Projects. This consolidation also makes financial sense,since we can concentrate and maximize efficient use of our behavioral expertise.The role of specific molecular targets in behavioral responses related to mood and motivation are tested witha variety of approaches, including advanced mouse mutagenesis and viral gene transfer in conjunction withthe Transgenic Core. The Behavioral Core then provides routine, relatively high throughput behavioral testsfor investigators in the Center's preclinical Projects (1-4). Encouraging findings are pursued with moresophisticated behavioral tests also via this Core. In addition, the Core obtains routine neuroendocrinemeasurements (e.g., plasma corticosterone levels) and antidepressant blood levels in behaving animals asneeded for particular experiments.
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