P. Nestby et al., Unrestricted free choice ethanol self-administration in rats causes long term neuroadaptations in the nucleus accumbens and caudate putamen, PSYCHOPHAR, 141(3), 1999, pp. 307-314
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.