Risk preference following adolescent alcohol use is associated with corrupted encoding of costs but not rewards by mesolimbic dopamine

Abstract

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.

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

“…Daily adolescent alcohol intake was stable across the 20-day exposure period (F (19,266) day = 1.62, NS) and averaged 11.5 ± 0.98 g/kg, comparable to our previous studies ( Figure 1b; Nasrallah et al, 2011;Schindler et al, 2014). The caloric intake was comparable for alcohol-and controlexposed animals (F (6,172) day × group = 1.69, NS; F (1,29) group = 0.184, NS) and both groups increased in body weight to the same extent over the course of the 20-day exposure period (Figure 1c; F (1,35) day × group = 1.57, NS; F (1,29) group = 1.48, NS).…”

“…Importantly, a previous study in which rats were pair-housed and exposed to intragastric alcohol or control administration during adolescence observed that alcohol-treated animals showed increased lever-pressing behavior during Pavlovian conditioning consistent with the results outlined here (McClory and Spear, 2014), indicating that the effects of alcohol on learning are consistent across housing conditions. Finally, our work demonstrating that adolescent alcohol promotes maladaptive decision making (Nasrallah et al, 2011;Schindler et al, 2014), findings that we have previously linked to learning effects similar to the ones found here (Clark et al, 2012), have been replicated in animals that were group housed during intragastric alcohol administration in adolescence (Boutros et al, 2014). Thus the observed increase in sign-tracking behavior reported here is most likely the result of alcohol exposure rather than housing conditions.…”

“…We have previously shown that moderate adolescent alcohol consumption in rats promotes suboptimal risk preference and a corresponding increase in striatal dopamine release in response to risky choices in adulthood (Nasrallah et al, 2011). We have further demonstrated that increased risk preference may result from a selective defect in reinforcement learning (Clark et al, 2012) and that this is a specific consequence of alcohol exposure during adolescence, as identical exposure in adults does not produce this effect (Schindler et al, 2014).…”

“…Alcohol, similar to virtually all abused substances, increases dopamine transmission within the ventral striatum (Cheer et al, 2007;Di Chiara and Imperato 1986;. Importantly, the mesolimbic dopamine system continues to mature during the adolescent period (Chambers et al, 2003), suggesting that adolescent alcohol use may alter its function, resulting in abnormal reward-related learning processes that impact decision making (Alaux-Cantin et al, 2013;Casey and Jones 2010;Goudriaan et al, 2007;Johnson et al, 2008;McClory and Spear 2014;Nasrallah et al, 2011;Philpot et al, 2009;Toalston et al, 2014;Zeigler et al, 2005).…”

Decision Making Across the Life Span

“…In addition, the activity of midbrain dopamine neurons encodes information regarding both reward probability and delay (Fiorillo et al, 2003;Kobayashi and Schultz, 2008), suggesting that this neurochemical system processes information regarding outcome costs. Consistent with this hypothesis, a recent study found that suboptimal increases in preference for the large risky reward in the probability discounting task in a chronic ethanol exposure model were associated with a failure of mesolimbic dopamine activity to encode information about risk of reward omission (Nasrallah et al, 2011). Given that dopaminergic neurotransmission is attenuated with age (Burwell et al, 1995;Kaasinen and Rinne, 2002), it is possible that reductions in dopaminergic encoding of reward costs could account for the increased preference for the risky reward in some rats in the present study.…”