Rates of drug abuse in the United States vary considerably over time and from place to place. However, the past thirty years or so have seen consistent patterns of drug abuse involving substances known to be (at least in part) inhibitors of dopamine neuronal uptake. In this proposal, we plan to determine how dopamine release and uptake rates are affected by drugs of abuse on the time scale of neuronal function (milliseconds). This information is needed in order to better understand how the spatial and temporal characteristics of dopaminergic neuronal chemical signaling are altered by drugs of abuse. The work proposed will: (1) refine newly developed techniques for the measurement of endogenous release and reuptake rates and rate constants on the millisecond time scale in vitro (using a rotating disk electroanalytical technique) and in vivo (using in vivo voltammetry), (2) determine how dopamine receptors, biosynthesis, biodegradation, and intracellular localization of dopamine influences the measured rates and rate constants, (3) determine how acute and chronic administration drugs of abuse (amphetamine and cocaine) will affect the rates measured, and (4) compare the results obtained with other dopamine blockers (bupropion, nomifensine, benztropine, and GBR-12909. The animal model in these studies is the rat because much of the experimental behavior and biochemical work related to drug abuse has been conducted with this animal.
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