Opioid influences on ethanol reward and aversion

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DESCRIPTION (provided by applicant): Opioid antagonists have been used in the treatment of alcoholism. This treatment is somewhat effective, however, the mechanisms responsible for its success remain unknown. The long-term goal of this research is to determine the mechanisms of action by which opioid antagonists alter the motivational effects of ethanol in order to develop more effective treatments for alcoholism. Previous studies have attempted to localize the effects of naloxone on ethanol drinking and the development of naloxone induced conditioned place aversion, none have localized the effects of naloxone on the expression of conditioned effects of ethanol. Further, the doses of naloxone that are behaviorally effective are far greater than those required to block opioid receptors, which might indicate that the effects of naloxone are not specific to opioid receptors. The proposed project seeks to first determine what brain areas modulate the effects of naloxone on the expression of conditioned ethanol effects. Specifically, intra-nucleus accumbens and ventral tegmental area injections of methylnaloxonium will be made in mice after they have undergone conditioning for ethanol place preference or aversion and prior to test sessions for conditioned place preference. Once a site of action is identified, future experiments will examine the effects of subtype selective antagonists.