During the previous funding period we have focused our efforts on the acute actions of ethanol on the rodent hippocampus, a brain area known to be highly sensitive to intoxicating doses of ethanol. The relevance of investigating this structure has been supported by the acute and chronic actions of ethanol on cognitive processes believed to be mediated by this structure. Our most recent work has uncovered regionally specific actions of ethanol in different cell fields of the hippocampus and has provided further evidence for the role of hippocampal GABA-containing interneurons in mediating the effects of ethanol in the dentate gyrus of the intact rat. We are continuing and refocusing these investigations in a separate ROI application to NIAAA. The present application is an expanded experimental effort toward the focus of the last Specific Aim of the previously funded ARC application. That is, we will now concentrate our efforts on the neuropharmacology of ethanol on a separate but related limbic brain structure, the nucleus accumbens (NAcc). There is a growing consensus that the nucleus accumbens (NAcc) neuronal complex located in the basal forebrain of mammals may be part of the final -common pathway resulting in drug reinforced behavior. Through both direct and indirect actions, drugs of abuse including psychostimulants and opiates are proposed to alter as yet obscure processes in this structure, leading to the increased probability of self-administration of these drugs. Recent evidence now lends credence to the hypothesis that ethanol's reinforcing effects are potentially mediated by components of this same neuronal circuit. The overall objective of this renewal application is to investigate the electrophysiological consequences of acute, intoxicating doses of ethanol on intact central nervous system circuitry believed to be critical for the reinforcing consequences of ethanol ingestion. This circuitry, including the nucleus accumbens and the ventral tegmental area of Tsai (VTA) in the midbrain will be investigated using extracellular electrophysiological methodologies in both the anesthetized as well as in the ethanol self-administering, unrestrained rat. These studies will constitute the first investigations to analyze the electrophysiological correlates of intoxicating doses of ethanol on the nucleus accumbens and will provide a comparison for which to view the cellular effects of other drugs of abuse on this structure. The hypothesis that dopamine projections from the VTA and/or reciprocal feedback from the NAcc are essential for the effects of ethanol on NAcc activity will be evaluated, as will the potential roles of other neurotransmitter candidates of both extrinsic as well as intrinsic origin including glutamate, serotonin and potentially other neuropeptides such as the opioids and somatostatin. Finally, we will evaluate whether chronic ethanol exposure alters the electrophysiological and neuropharmacological interactions established in the acute studies described above.
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