UC San Diego

Chronic, high-level exposure to alcohol is associated with deficits in adaptive behavior, or the ability to flexibly adjust actions to achieve desirable outcomes. Such deficits can broadly impact quality of life, for instance by perpetuating alcohol consumption despite increasingly negative consequences. However, the specific components of adaptive behavior that are disrupted following chronic alcohol exposure are not entirely clear. One aspect that may be affected is the ability to use the incentive value – essentially, the subjective attractiveness – of possible outcomes to guide actions. This dissertation examines this possibility across two tasks crucially dependent on the use of incentive value, and investigates the contribution of central amygdala (CeA), a brain region implicated in incentive processes. Chapter 1 examined the ability of mice previously exposed to chronic alcohol to update and use incentive value of food following a shift in motivational state. Results found alcohol mice were impaired following a mild shift in motivation but less so following a large shift, suggesting that deficits could be largely overcome with a salient enough motivational change. Chapter 2 examined the effect of incentive food cues on the actions of mice with a history of chronic alcohol exposure. Results found that the behavior of alcohol mice was subject to greater control by incentive cues, suggesting that the use of incentive value was enhanced in these animals. Chapter 3 examined this same cue-guided behavior during manipulation of CeA activity. Results suggested that alcohol enhancements in cue-guided behavior were countered by excitatory manipulation of CeA, but that CeA manipulation had opposite behavioral effects in alcohol-naïve mice. Together, these studies support that chronic alcohol exposure may enhance the use of incentive value in some circumstances but impair that ability in others, depending on crucial task features. Further, these findings suggest that a nuanced combination of major theories of addiction, such as the negative reinforcement and habit hypotheses, may be warranted. Greater understanding of how chronic alcohol exposure can impact behavior and the brain may prove useful in developing improved assessments and treatments for chronic alcohol use and alcohol use disorder in humans.