ETHANOL SELF-ADMINISTRATION RESTORES WITHDRAWAL-ASSOCIATED DEFICIENCIES IN ACCUMBAL DOPAMINE AND 5-HYDROXYTRYPTAMINE RELEASE IN DEPENDENT RATS

Basal forebrain dopamine (DA) and 5-HT neurotransmission has been impl icated in the mediation of the acute reinforcing actions of ethanol. N euroadaptation theories predict that compensatory changes in neurochem ical systems that are activated by alcohol acutely may underlie sympto ms of withdrawal after chronic administration. To test this hypothesis , the release of DA and 5-HT was monitored by microdialysis in the nuc leus accumbens of dependent male Wistar rats at the end of a 3-5 week ethanol (8.7% w/v) liquid diet regimen, during 8 hr of withdrawal, and during renewed availability of ethanol involving (1) the opportunity to operantly self-administer ethanol (10% w/v) for 60 min, followed by (2) unlimited access to the ethanol-liquid diet. Results were compare d to control groups pair-fed with ethanol-free liquid diet and trained to self-administer either ethanol or water. In nondependent rats, ope rant ethanol self-administration increased both DA and 5-HT release in the NAG. Withdrawal from the chronic ethanol diet produced a progress ive suppression in the release of these transmitters over the 8 hr wit hdrawal period. Self-administration of ethanol reinstated and maintain ed DA release at prewithdrawal levels but failed to completely restore 5-HT efflux. 5-HT levels recovered rapidly, however, within 1 hr of r eexposure to ethanol liquid diet. These findings suggest that deficits in accumbal monoamine release may contribute to the negative affectiv e consequences ethanol withdrawal and, thereby, motivate ethanol-seeki ng behavior in dependent subjects.