Ethanol administration potentiates cocaine-induced dopamine levels in the rat nucleus accumbens

Ethanol and cocaine are frequently co-abused, and the drug combination has been reported to produce an increased and prolonged subjective euphoria as compared to when either drug is administered alone. Acute administration of ethanol or cocaine increases the extracellular dopamine (DA) concentration in the nucleus accumbens (NAcc), a terminal region of the mesolimbic dopaminergic pathway. In the present study, the effects of separate and concurrent administration of cocaine and ethanol on DA concentrations in the NAcc were studied in rats pretreated with ethanol. Four groups of rats received either ethanol (2 g/kg, i.p.) or saline twice daily for 6 consecutive days. Thereafter, rats were given injections of saline or cocaine for another 2 days (i.e. treatment days 7 and 8) using a 'binge' administration pattern (three i.p. injections of 15 mg/kg each with 1-h interval starting 40 min after the first of the two daily doses of ethanol/saline). Stereotypic behavior was scored after each 'binge' of cocaine or saline on days 7 and 8. The DA and DA metabolite concentrations were measured using microdialysis on day 8. Ethanol enhanced the effect of cocaine on DA concentration in the NAcc as compared to a single administration of cocaine. The DA levels increased and reached their maximum values within 20-40 min after the cocaine administration, then gradually declined until the next injection 1-h later. Cocaine-induced stereotypic behavior was significantly increased in both saline and ethanol pretreated groups, though there was no significant difference between the two groups. The results of this study suggest that the enhanced DA transmission may be related to the experience produced by concurrent abuse of ethanol and cocaine in humans.