The mechanisms that underlie the development of ethanol reinforcement are not fully understood, but the involvement of dopamine in the mesocorticolimbic system has been hypothesized for some time. It is clear that ethanol administration stimulates dopamine release in this system, but the role of dopamine during various phases of the development of ethanol reinforcement is unclear. Studies done in the last grant period show that dopamine activity undergoes plasticity during the development of the reinforcing properties of ethanol such that a transient increase in accumbal dopamine occurs during consumption of ethanol after a few days of exposure to ethanol, but not during an initial exposure. This transient increase in dopamine is correlated with exposure to the stimulus properties of ethanol rather than the brain concentration of ethanol. Recent work has implicated the role of subregions of the nucleus accumbens (core and shell) as having different functional roles in natural and drug reward. Also, the prefrontal cortex is known to be involved in motivated behavior such as drug seeking behavior. Therefore, we hypothesize that the development of ethanol reinforcement is mediated by the enhancement of dopamine activity in these various brain areas at various times during the development ethanol reinforcement.
The specific aims of the proposal are to determine (1) the effect of ethanol consumption on dopamine release in vivo in the prefrontal cortex and nucleus accumbens (core and shell) of Long Evans rats at early phases in the development of reinforcement, (2) the effects of ethanol through i.v. administration on extracellular dopamine in the mesocorticolimbic system during an initial exposure to ethanol in the drinking solution, and (3) whether the taste and smell of ethanol contribute to the transient dopamine response observed during oral ethanol consumption. Together the experiments proposed will provide new data on the role of dopamine in the early stages of the development of ethanol reinforcement in a behaviorally relevant context.
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