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 dopam inergic pathway. In the present study, the effects of separate and concurre nt administration of cocaine and ethanol on DA concentrations in the NAcc w ere studied in rats pretreated with ethanol. Four groups of rats received e ither 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 d ays (i.e. treatment days 7 and 8) using a 'binge' administration pattern (t hree i.p. injections of 15 mg/kg each with I-h interval starting 40 min aft er the first of the two daily doses of ethanol/saline). Stereotypic behavio r was scored after each 'binge' of cocaine or saline on days 7 and 8. The D A 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 adminis tration, then gradually declined until the next injection 1-h later. Cocain e-induced stereotypic behavior was significantly increased in both saline a nd ethanol pretreated groups, though there was no significant difference be tween the two groups. The results of this study suggest that the enhanced D A transmission may be related to the experience produced by concurrent abus e of ethanol and cocaine in humans. (C) 2001 Elsevier Science BY All rights reserved.