Several emerging theories of addiction have described how abused substances exploit vulnerabilities in decision-making processes. These vulnerabilities have been proposed to result from pharmacologically corrupted neural mechanisms of normal brain valuation systems. High alcohol intake in rats during adolescence has been shown to increase risk preference, leading to suboptimal performance on a decision-making task when tested in adulthood. Understanding how alcohol use corrupts decision making in this way has significant clinical implications. However, the underlying mechanism by which alcohol use increases risk preference remains unclear. To address this central issue, we assessed dopamine neurotransmission with fast-scan cyclic voltammetry during reward valuation and risk-based decision making in rats with and without a history of adolescent alcohol intake. We specifically targeted the mesolimbic dopamine system, the site of action for virtually all abused substances. This system, which continuously develops during the adolescent period, is central to both reward processing and risk-based decision making. We report that a history of adolescent alcohol use alters dopamine signaling to risk but not to reward. Thus, a corruption of cost encoding suggests that adolescent alcohol use leads to long-term changes in decision making by altering the valuation of risk.

Individuals who abused alcohol at an early age show decisionmaking impairments. However, the question of whether maladaptive choice constitutes a predisposing factor to, or a consequence resulting from, alcohol exposure remains open. To examine whether a causal link exists between voluntary alcohol consumption during adolescence and adult decision making the present studies used a rodent model. High levels of voluntary alcohol intake were promoted by providing adolescent rats with access to alcohol in a palatable gel matrix under nondeprivation conditions. A probability-discounting instrumental response task offered a choice between large but uncertain rewards and small but certain rewards to assess risk-based choice in adulthood either 3 weeks or 3 months following alcohol exposure. While control animals' performance on this task closely conformed to a predictive model of risk-neutral value matching, rats that consumed high levels of alcohol during adolescence violated this model, demonstrating greater risk preference. Evidence of significant risk bias was still present when choice was assessed 3 months following discontinuation of alcohol access. These findings provide evidence that adolescent alcohol exposure may lead to altered decision making during adulthood and this model offers a promising approach to the investigation of the neurobiological underpinnings of this link.adolescence ͉ probability discounting A dolescent alcohol use is a serious public health problem and is associated with an increased risk for development of chronic alcohol use disorders in adulthood (1). Furthermore, an association between a history of alcohol abuse and deficits in decision making has been documented (2-5). However, the question of whether maladaptive choices constitute a predisposing factor to, or a consequence resulting from, alcohol use remains open. Animal models allow for direct testing of causality and for examination of potential neural substrates underlying an association between alcohol use and risky decision making.Developing rodent models of alcohol abuse has been challenged by the fact that most rat strains do not freely consume significant amounts of ethanol in solution. A method for overcoming the reluctance of nondeprived rats to drink high levels of ethanol in solution was developed by Rowland et al. (6). It utilizes a palatable gel matrix containing ethanol and when made available to rats it stimulates robust and reliable selfadministration, without the need for fluid or food deprivation or any training period. Intake of these alcohol ''Jello Shots'' resulted in significant elevations of blood alcohol concentrations (6) in the range of 5 to 45 mg % with a linear relationship to amount consumed (r ϭ 0.94). Furthermore, alterations in brain chemistry in association with this administration protocol have also been documented (7-8). Since this delivery method does not require training to promote intake, it is particularly appropriate for developmental studies, such as those focused on adolescence, since, in ro...

Alcohol use during adolescence has profound and enduring consequences on decision-making under risk. However, the fundamental psychological processes underlying these changes are unknown. Here, we show that alcohol use produces over-fast learning for better-than-expected, but not worse-than-expected, outcomes without altering subjective reward valuation. We constructed a simple reinforcement learning model to simulate altered decision making using behavioral parameters extracted from rats with a history of adolescent alcohol use. Remarkably, the learning imbalance alone was sufficient to simulate the divergence in choice behavior observed between these groups of animals. These findings identify a selective alteration in reinforcement learning following adolescent alcohol use that can account for a robust change in risk-based decision making persisting into later life.

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The present studies examine some parameters involved in flavor avoidance learning, using LiCl to induce malaise, in a novel nondeprivation protocol that allows direct comparison between rats and mice. The procedure involves daily presentation of a gelatin dessert that contains carbohydrate (Polycose) and a distinctive food flavor. Regular chow is additionally available at all times. Both rats and mice showed robust intakes of these gels with little change of gram intake as concentration of Polycose was varied in the range 2-30%; at the highest concentration, the caloric yield was approximately 7% of normal daily intake in both species. Rats that were injected on three occasions with LiCl (0.75 meq/kg) 1 h after consumption of a flavored gel formed a complete and sustained conditioned flavor avoidance (CFA). In a two-flavor discrimination protocol, in which a second flavor was followed by injections of saline, rats showed complete avoidance of the LiCl-paired flavor and partial avoidance of the saline-paired flavor. Mice injected on three occasions with LiCl (6 meq/kg) 1 h after intake of a flavored gel formed a partial CFA; a more complete CFA was formed when there was no delay between removal of the flavor and the injection. Using this no-delay protocol, mice, like rats, showed avoidance of a saline-paired flavor in a two-flavor discrimination protocol, and the CFA was strong when the dose of LiCl was reduced to that used in rats (0.75 meq/kg). In comparable protocols, mice thus are able to form complete CFAs using low doses of LiCl that are comparable to CFAs observed in rats, but the interval between flavor and sickness over which associative learning can occur may be shorter in mice.