The ultimate goal of this proposed research is to understand the role of brain neurotransmitter systems in the actions of psychotropic drugs and in the maintenance of behavior. The research will focus on the behavioral involvement of dopamine, norepinephrine, and 5-hydroxytryptamine. Behavior will be measured using a computer-controlled real-time data application system. The research will employ two closely related parallel approaches. In the first approach, a sensitive and specific operant behavioral screen that detects drugs with antidepressant action will be used to determine the catecholaminergic and serotonergic components of antidepressant drugs effects. Also, studies will be done to determine whether norepinephrine, dopamine and 5-hydroxytryptamine systems interact to produce antidepressant effects. The goal of this research is to elucidate the neurochemical changes that mediate antidepressant drug effects on operant behavior. Knowledge of these neurochemical changes could provide insight into the pathophysiology of depression. For the second approach, studies will be done to determine the neurochemical mechanisms that mediate interactions between drugs, behavior and the environment. Drug effects on behavior depend not only on the specific drug and dose of the drug, but also depend on the environment in which the drug is administered and on the ongoing behavior. Therefore, neurochemical change will be measured as a function of systematically varied environmental and behavioral parameters. Knowledge of environmental and behavioral parameters as independent variables that alter brain chemistry would provide additional insight into the pathophysiology of mental illness.
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