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

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. OBJECTIVES: We investigated the impact of adolescent binge-like alcohol on phasic dopaminergic neurotransmission during adulthood. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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

Adolescent Alcohol Exposure Amplifies the Incentive Value of Reward-Predictive Cues through Potentiation of Phasic Dopamine Signaling

Adolescent alcohol use remains a major public health concern due in part to well-established findings implicating the age of onset in alcohol use in the development of alcohol use disorders and persistent decision making deficits in adults. We have previously demonstrated that moderate adolescent alcohol consumption in rats promotes suboptimal decision making and an associated perturbation in mesolimbic dopamine transmission in adulthood. Dopamine-dependent incentive learning processes are an integral component of value-based decision making and a fundamental element to many theoretical accounts of addiction. Thus, we tested the hypothesis that adolescent alcohol use selectively alters incentive learning processes through perturbation of mesolimbic dopamine systems. To assess incentive learning, behavioral and neurochemical measurements were made during the acquisition, maintenance,extinction, and reacquisition of a Pavlovian conditioned approach procedure, in adult rats with a history of adolescent alcohol consumption. We show that moderate adolescent alcohol consumption potentiates stimulus-evoked phasic dopamine transmission, measured in vivo by fast-scan cyclic voltammetry, in adulthood and biases individuals toward a dopamine-dependent incentive learning strategy. Moreover, we demonstrate that animals exposed to alcohol in adolescence are more sensitive to an unexpected variation in reward outcomes. This pattern of phasic dopamine signaling and the associated bias in learning may provide a mechanism for the well documented vulnerability of individuals with early-life alcohol use for alcohol use disorders in adulthood