Chunk #32 — 3 Neural Substrates for the Negative Emotional State Associated with Alcoholism — 3.1 Within-System Neuroadaptations that Contribute to the Compulsivity Associated with the Dark Side of Alcoholism
More compelling in the mesolimbic dopamine domain are the decreases in activity of the mesolimbic dopamine system and decreases in serotonergic neurotransmission in the nucleus accumbens that occur during alcohol withdrawal in animal studies (Rossetti et al. 1992; Weiss et al. 1992a, 1996). In dependent male Wistar rats trained to self-administer ethanol during withdrawal, the release of dopamine and serotonin was monitored by microdialysis in the nucleus accumbens at the end of a 3–5 week ethanol (8.7% w/v) liquid diet regimen, during 8 h of withdrawal, and during renewed availability of ethanol involving the opportunity to operantly self-administer ethanol (10% w/v) for 60 min, followed by unlimited access to the ethanol liquid diet. In nondependent rats, operant ethanol self-administration increased both dopamine and serotonin release in the nucleus accumbens. Withdrawal from the chronic ethanol diet produced a progressive suppression in the release of these transmitters over the 8 h withdrawal period. Self-administration of ethanol reinstated and maintained dopamine release at pre-withdrawal levels but failed to completely restore serotonin efflux. These findings suggested that deficits in nucleus accumbens monoamine release may
