Effects of Ethanol Exposure on Mesolimbic Dopamine

Wake Forest University Health Sciences, Winston-Salem NC

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Abstract

DESCRIPTION (provided by applicant): Ethanol is a widely abused, reinforcing drug. Researchers have long aimed to elucidate the mechanisms of ethanol action in the brain. Considerable advances have been made in identifying the neural substrates that mediate the reinforcing actions of ethanol. In fact, the hypothesis that dopamine (DA), and specifically elevated DA in the nucleus accumbens (Nac), is involved in ethanol reinforcement is widely accepted. However, many questions remain about the neurochemical consequences of these DA changes. The goal of the proposed study is to further investigate the influence of chronic ethanol on dopaminergic signaling in the brain using a new experimental tool. Fast-scan cyclic voltammetry, allowing extremely sensitive spatial and temporal measurements of extracellular DA, will be used to directly assess the consequences of chronic ethanol on DA release and uptake in the Nac of freely moving rats. We will test the hypothesis that chronic ethanol exposure leads to adaptations in dopaminergic transmission aimed at decreasing dopamine signaling. We expect that chronic ethanol exposure will induce a substantial suppression of DA release, leading to a compensatory decrease of DA uptake. In any case, the results of this study will provide valuable information on the modulation of dopaminergic neurotransmission by chronic ethanol.