Alcohol, stress, and decision making

Alcoholism is enormously costly to both individuals and society, and alcoholics suffer from high rates of relapse. Both acute and chronic alcohol consumption contribute to impulsive choice, or the preference for immediate rewards, even when delayed rewards are more valuable. The research presented here is divided into two sections that address different aspects of the relationship between alcohol (ethanol) consumption and impulsivity. Although it has been established that acute ethanol administration causes impulsivity, theneural mechanisms underlying these effects have not been examined. Chapter 2 describes in vivo electrophysiology studies that investigated the effect of acute ethanol administration on neural encoding in the nucleus accumbens (NAcc) core during decision making tasks. The NAcc mediates delay-based decision making and receives direct projects from the ventral tegmental area (VTA), which has widely been implicated in addiction. The data presented here show thatincreases in NAcc firing in response to reward-predictive cues encode the value of the anticipated reward, and ethanol impairs this encoding. Moreover, ethanol selectively suppresses operant (lever press)-related firing for delayed rewards. This suppression is accompanied by a selective increase in behavioral response latency when delayed rewards are anticipated. Both the loss of cue-evoked value encoding and the selective decrease in lever press-evoked firing suggest a neural mechanism by which ethanol-induced changes in NAcc encoding contribute to impulsivity. Acute stress contributes to relapse in humans and reinstatement in animal models, and one way in which this may occur is by causing organisms to become more impulsive, leading to a preference for immediate alcohol reward over the long-term benefits of abstinence. Chapter 3 describes behavioral pharmacology experiments that examined the effect of the pharmacologicalstressor yohimbine and three other noradrenergic receptor-specific manipulations (propranolol, guanfacine, and prazosin) on impulsive choice using a delay discounting task. Rather than affecting impulsivity per se, acute pharmacological stress promoted inflexible behavior at the expense of flexible, goal-directed behavior, while the other three manipulations had no effect onreward preference. Further studies are necessary to examine the extent to which these findings apply to alcohol-seeking behaviors.