Unrestricted free choice ethanol self-administration in rats causes long term neuroadaptations in the nucleus accumbens and caudate putamen

In the present study, the reactivity of striatal dopamine and dopamine-sens itive neurons in superfused striatal slices of ethanol-experienced rats was compared to that of ethanol-naive rats, 3 weeks after oral ethanol self-ad ministration. During the acquisition phase (17 days), rats were offered inc reasing concentrations of ethanol (from 2 to 10%, 24 h per day) on an alter nate-day schedule in a free choice with water. Following 2 weeks of unrestr icted 10% ethanol consumption, the highest and lowest drinkers (representin g about 25% of the upper and lower extremes of the total population) were s elected. Preliminary experiments revealed that both groups of rats displaye d a profound increase in ethanol consumption and preference 3 weeks after c essation of ethanol self-administration (deprivation effect). This deprivat ion effect was associated with an increase in electrically evoked release o f [H-3]dopamine from superfused nucleus accumbens slices, whereas the evoke d [H-3]dopamine release from caudate putamen slices remained unchanged. In slices of the caudate putamen, but not in nucleus accumbens slices, postsyn aptic dopamine D-1 receptor-stimulated cyclic AMP production was also enhan ced. In addition, prior ethanol consumption enhanced the electrically evoke d release of [C-14]acetylcholine release in both striatal regions. Interest ingly, the magnitude of these long-term neuroadaptations correlated with th e amount of daily ethanol consumption, i.e. neuronal hyperresponsiveness in the striatum was more profound in the high than in the low ethanol drinker s. These data show for the first time that unrestricted free-choice ethanol consumption in rats is associated with a longterm increase in dopaminergic and cholinergic neurotransmission in the nucleus accumbens and caudate put amen. These (and other) neuroadaptations may underlie the enhanced motivati on to self-administer ethanol and the maintenance of ethanol consumption lo ng after deprivation.