BEHAVIOR AND MECHANISM IN ACUTE AMPHETAMINE WITHDRAWAL

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Rats are hypoactive 20 hours after receiving a moderate dose of amphetamine. This hypo-activity may indicate the presence of an acute withdrawal state and of a low-grade depression. The purpose of the research is to develop an animal model of acute withdrawal and to use it to investigate mechanisms and treatments. Methods. In the past year we have continued to develop behavioral procedures designed to provide converging evidence for the presence of acute withdrawal 20 hours after amphetamine treatment: We assessed working for food (appetitive behavior) and consuming food (consummatory behavior) at different times following amphetamine treatment. In order to evaluate whether amphetamine produces longer-term hypoactivity by initially activating dopamine receptors, we continued to look at the ability of pre-treatment with dopamine receptor antagonists to block amphetamine-induced hypoactivity. In order to identify molecular events that might mediate amphetamine's effects, we used real-time PCR to look at changes in gene expression (prodynorphin, D1 receptor, D2 receptor) in several brain regions at different times following treatment.