PPG investigators are studying numerous genes and their protein products in the brain's reward circuits to define their role in drug abuse and addiction. To accomplish this goal, the Behavioral Core has established a broad battery of behavioral tests in rats and mice. This battery includes relatively routine, high throughput tests, including assays of locomotor activity and sensitization, conditioned place preference and aversion, opiate withdrawal, analgesia, and sucrose preference, to name a few. In addition, several more complex paradigms are available in the Core, such as the 5-choice serial reaction time test and other cognitive assays, as well as operant responding for food or sucrose. Conditioned reward and intracranial self-stimulation assays are made available to Project investigators via outside subcontracts. 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 are able to infer, with much greater accuracy, the role of a given gene in complex behavior related to addiction. By consolidating these behavioral tests within a centralized Core, we 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 genes and proteins in behavioral responses related to drug abuse and addiction is tested with a variety of experimental approaches, including advanced mouse mutagenesis and viral gene transfer in conjunction with the Transgenic Core. We 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 or other mutants of the protein;and 3) mutant mice that lack or overexpress the target protein or a dominant negative mutant. The latter includes 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 then provides routine, high throughput behavioral tests for investigators in the individual Projects. Encouraging findings are pursued with the more sophisticated behavioral tests also available in the Core and with drug self-administration and relapse assays in conjunction with Project 4. Finally, the Core obtains routine plasma drug levels or related measurements (e.g., plasma corticosterone, electrolyte levels) in behaving animals as needed for particular experiments.
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