Adolescent binge-like alcohol alters sensitivity to acute alcohol effects on dopamine release in the nucleus accumbens of adult rats.

Abstract

Rationale: Early onset of alcohol drinking has been associated with alcohol abuse in adulthood. The neurobiology of this phenomenon is unclear, but mesolimbic dopamine pathways, which are dynamic during adolescence, may play a role. We investigated the impact of adolescent binge-like alcohol on phasic dopaminergic neurotransmission during adulthood. Rats received intermittent intragastric ethanol, water, or nothing during adolescence. In adulthood, electrically evoked dopamine release and subsequent uptake were measured in the nucleus accumbens core at baseline and after acute challenge of ethanol or saline. Adolescent ethanol exposure did not alter basal measures of evoked dopamine release or uptake. Ethanol challenge dose-dependently decreased the amplitude of evoked dopamine release in rats by 30–50 % in control groups, as previously reported, but did not alter evoked release in ethanol-exposed animals. To address the mechanism by which ethanol altered dopamine signaling, the evoked signals were modeled to estimate dopamine efflux per impulse and the velocity of the dopamine transporter. Dopamine uptake was slower in all exposure groups after ethanol challenge compared to saline, while dopamine efflux per pulse of electrical stimulation was reduced by ethanol only in ethanol-naive rats. The results demonstrate that exposure to binge levels of ethanol during adolescence blunts the effect of ethanol challenge to reduce the amplitude of phasic dopamine release in adulthood. Large dopamine transients may result in more extracellular dopamine after alcohol challenge in adolescent-exposed rats and may be one mechanism by which alcohol is more reinforcing in people who initiated drinking at an early age.