Center investigators are studying numerous genes and their protein products in the brain's appetitive circuits to define their role in the regulation of mood and motivation under normal circumstances and in animal models of depression and antidepressant action. To accomplish this goal, the Behavioral Core has established a broad battery of behavioral tests in rats and mice. This battery includes several routine measures of locomotor activity and anxiety-Iike behavior, as well as several depression-related tests such as the forced swim test and learned helplessness paradigm. The battery also incorporates several additional tests that provide complementary information about an animal's affective state; these include measures of fear conditioning, sexual behavior, incentive motivation for food, intra-cranial self-stimulation, and social interaction, to name some examples. In addition, Core personnel will continually work to extend this battery to additional tests in the years ahead. The imperative to employ such a large battery of behavioral tests is that it is 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 will be able to infer, with much greater accuracy, the role of a given gene in complex behavior related to depression. By consolidating these behavioral tests within a centralized Core, we can ensure rigorous control over the data as well as facilitate comparisons and contrasts 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 target proteins in behavioral responses related to mood and motivation will be tested with a variety of approaches, including advanced mouse mutagenesis techniques in conjunction with the Transgenic Core. We will utilize: 1) intracerebral injections of specific activators or inhibitors of a target protein; 2) intracerebral injections of viral vectors that overexpress the target protein itself or a dominant negative mutant of the protein; and 3) mutant mice that lack or overexpress the target protein or a dominant negative mutant. The latter will include mutant mice in which the target gene is overexpressed or knocked out in an inducible manner and selectively within a brain region of interest. The Behavioral Core will then provide routine, high throughput behavioral tests for investigators in the Center's Projects. Encouraging findings will be pursued with more sophisticated behavioral tests also via this Core. In addition, the Core will obtain routine neuroendocrine measurements (e.g., plasma corticosterone levels) in behaving animals as needed for particular experiments.
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