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Volume 16, Number 10, Issue of May 15, 1996 pp. 3474-3485
Copyright ©1996 Society for NeuroscienceEthanol Self-Administration Restores Withdrawal-Associated Deficiencies in Accumbal Dopamine and 5-Hydroxytryptamine Release in Dependent Rats
Received Nov. 2, 1995; revised Feb. 23, 1996; accepted Feb. 28, 1996.
Friedbert Weiss, Loren H. Parsons, Gery Schulteis, Petri Hyytiä, Marge T. Lorang, Floyd E. Bloom, and George F. Koob Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037
Basal forebrain dopamine (DA) and 5-HT neurotransmission has been implicated in the mediation of the acute reinforcing actions of ethanol. Neuroadaptation theories predict that compensatory changes in neurochemical systems that are activated by alcohol acutely may underlie symptoms of withdrawal after chronic administration. To test this hypothesis, the release of DA and 5-HT was monitored by microdialysis in the nucleus 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 compared to control groups pair-fed with ethanol-free liquid diet and trained to self-administer either ethanol or water. In nondependent rats, operant ethanol self-administration increased both DA and 5-HT release in the NAC. Withdrawal from the chronic ethanol diet produced a progressive suppression in the release of these transmitters over the 8 hr withdrawal period. Self-administration of ethanol reinstated and maintained DA release at prewithdrawal levels but failed to completely restore 5-HT efflux. 5-HT levels recovered rapidly, however, within 1 hr of reexposure to ethanol liquid diet. These findings suggest that deficits in accumbal monoamine release may contribute to the negative affective consequences ethanol withdrawal and, thereby, motivate ethanol-seeking behavior in dependent subjects.
Key words: ethanol; dopamine; 5-HT; microdialysis; nucleus accumbens; self-administration; dependence; withdrawal; reinforcement
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