CNS Sites Mediating Alcohol Drinking Behavior

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DESCRIPTION (provided by applicant): The objectives of this research are to investigate dopamine (DA) regulation of alcohol drinking behavior within central nervous system (CMS) sites of the mesocorticolimbic DA system that are thought to mediate ethanol drinking and drug reward, and to examine the neuronal alterations on DA neurotransmission in these areas that occur as a result of ethanol exposure. Recent evidence strongly implicates specific neuroanatomical circuits and subcircuits in drug reward. The structures that make up these circuits are components of the mesocorticolimbic DA system. Some of the areas most clearly implicated in the rewarding effects of ethanol and other drugs of abuse include the posterior ventral tegmental area (VTA), the nucleus accumbens (NAc), the ventral pallidum (VP), and aspects of the medial prefrontal cortex (MPF). Recent evidence also shows that: (1) DA receptors play important mediating roles in ethanol self- administration within a number of these areas; (2) the rewarding effects of the direct application of ethanol into the VTA appear to be mediated, at least partly, through DA receptors; and (3) the self-administration of ethanol alters DA neurotransmission and produces "neuroadaptations" in receptors that regulate the DA release as measured by extracellular levels of DA in the NAc. The proposed work will continue and extend studies on how ethanol self-administration alters DA neurotransmission within the VP, the shell and core of the NAc, the MPF, and the anterior and posterior VTA. The reinforcing effects of ethanol in different VTA DA projection regions will be investigated for involvement in mediating alcohol drinking. The studies also seek to determine the involvement of D1, D2 and/or 5 HT3 receptors within the VTA (anterior and posterior), NAc (shell and core) and VP on scheduled access ethanol drinking, and experiments are proposed to examine the involvement of other VTA DA projection regions in regulating alcohol drinking. The results of these studies will provide valuable information toward understanding the role of DA within the mesocorticolimbic DA system in alcohol drinking. Such information would be important for basic understanding of CNS circuitries involved in ethanol drinking behavior and how these circuits may adapt to the continued presence of ethanol. The findings should also be relevant to future development of therapeutic approaches, particularly pharmacotherapies, for the treatment of alcoholism and alcohol abuse.