Dissociation between the time course of ethanol and extracellular dopamineconcentrations in the nucleus accumbens after a single intraperitoneal injection

Background: Dopamine release in the nucleus accumbens has been linked to th e reinforcing effects of ethanol, but the time course or relationship of th is response to ethanol concentrations in the brain has not been studied. Methods: Various doses of ethanol (0-2.0 g/kg) were administered intraperit oneally to male Sprague Dawley(R) rats, and dopamine and ethanol were simul taneously analyzed in dialysate samples from the nucleus accumbens. A separ ate study to compare the ethanol-induced dopamine response in male and fema le rats was carried out by using a 1 g/kg intraperitoneal dose of ethanol. Results: In male rats, 1 and 2 g/kg ethanol significantly increased dialysa te dopamine by 40% over basal, whereas 0.25 and 0.5 g/kg ethanol produced a nonsignificant 20% increase. Dialysate ethanol concentrations exhibited a curvilinear decline after reaching peak levels for the lower doses but show ed a linear decrease after 1 and 2 g/kg. There was a dissociation between t he time courses of extracellular dopamine and ethanol after 1 and 2 g/kg et hanol treatment. The dopamine response returned to basal within 90 min, whe reas the ethanol concentrations remained elevated. In a separate study that compared male and female rats, the ratio of the dopamine response over bas al to the dialysate ethanol concentrations was significantly decreased at 6 0 min after an injection of 1 g/kg. However, there were no differences betw een males and females. Conclusions: The dissociation between dopamine and ethanol levers may refle ct the development of acute tolerance to ethanol-induced dopamine release i n the nucleus accumbens within the time course of a single acute injection. Given the strong links between dopamine and ethanol reinforcement, our fin dings may be relevant for understanding the time course of ethanol's reinfo rcing effects in vivo.