This research plan addresses the hypothesis that alcohol-induced activation of the opioid system is a neurobiological mechanism that contributes to high alcohol drinking. The goal of this proposal is to determine whether receptor-selective opioid antagonists are capable of blocking the initiation and maintenance of high alcohol drinking in rats selectively bred for alcohol preference. To achieve this goal the following specific aims will be pursued: 1. Determine whether chronic administration of a mu and a delta receptor-selective antagonist, alone and in combination, attenuates alcohol drinking after drinking has begun in rats selectively bred for alcohol preference. 2. Determine whether chronic administration of a mu or a delta receptor-selective antagonist prevents reinitiation of alcohol drinking following cessation of chronic consumption (relapse) in rats selectively bred for alcohol preference. 3. Determine whether chronic administration of a mu or a delta receptor-selective antagonist prevents the initiation of alcohol drinking in rats selectively bred for alcohol preference. The proposed experiments will determine the potency of mu and delta receptor-selective antagonists in attenuating alcohol intake and will determine whether these antagonists primarily reduce the intake of alcohol compared with the intake of food, water, and another preferred solution. The experiments will be conducted using rats of the alcohol-preferring (P) and high alcohol drinking (HAD) lines which are well suited for testing the efficacy of agents that have the potential to reduce alcohol intake.
| Froehlich, J C; Wand, G S (1997) Adenylyl cyclase signal transduction and alcohol-induced sedation. Pharmacol Biochem Behav 58:1021-30 |
