Dopaminergic neurotransmission in the nucleus accumbens may be an important factor in ethanol reinforcement and genetically determined ethanol preference. This hypothesis was tested by measuring dopamine (DA) release by intracranial microdialysis during voluntary oral ethanol self-administration in alcohol-preferring (P) and genetically heterogeneous Wistar rats. The animals were trained to respond for ethanol (10% w/v) or water in a free-choice operant task. Extracellular DA levels in the nucleus accumbens were subsequently monitored during 30-min self-administration sessions and a 15-min "waiting period" before session onset. Ethanol self-administration in all animals was followed by a significant, dose-dependent rise in DA release with maximal effects at approximately 15 min after peak intake. Dose-effect functions revealed significantly steeper slopes for the DA-releasing effects of ethanol in P than in genetically heterogeneous Wistar rats. Over an identical range of ethanol doses and blood alcohol levels, increases in DA efflux ranged from 143% to 459% of basal levels in P rats but only from 142% to 212% in Wistar rats. To differentiate the pharmacological effects of ethanol from the effects of operant responding, additional groups of P and Wistar rats were tested during self-administration of saccharin (0.05% w/v). By contrast with ethanol, saccharin did not substantially elevate extracellular DA levels. A significant, transient increase in DA efflux was, however, observed in both strains of rats during the presession waiting period in the absence of ethanol or saccharin availability.(ABSTRACT TRUNCATED AT 250 WORDS)