Effects of adolescent ethanol exposure on adult nondrug reward seeking behavior in male and female mice.

BACKGROUND: Adolescent alcohol use is associated with an increased likelihood of developing an alcohol use disorder in adulthood, potentially due to the effects of alcohol exposure on reward-seeking behavior. However, it remains unclear whether adolescent drinking is sufficient to alter nondrug reward seeking in adulthood. As adolescence is a period of both brain and sexual maturation, which occur in a sex-dependent manner, males and females may be differentially sensitive to the consequences of adolescent alcohol exposure. The present study investigated whether adolescent ethanol exposure affected food reward taking and seeking in male and female adult mice. METHODS: Male and female C57BL/6J mice underwent intermittent ethanol exposure (AIE) via vapor inhalation during early adolescence (28-42 days of age). At 10 weeks of age, the mice were trained in a conditioned place preference paradigm (CPP) for a food reward. We measured food consumption, CPP, and cFos expression in multiple brain regions following CPP testing. Data were analyzed using repeated measures analysis of variance with exposure (air vs. AIE), sex, and time as factors. RESULTS: AIE exposure increased food consumption during CPP training in adult male mice, but reduced pellet consumption in adult female mice. AIE exposure impaired CPP expression only in female mice. Despite these behavioral differences, exposure to the reward-paired chamber did not induce differential cFos expression following CPP testing in the prelimbic and infralimbic cortices or the nucleus accumbens core and shell. CONCLUSION: These findings indicate that adolescent ethanol exposure disrupted nondrug reward taking and seeking in adulthood in female mice and altered consumption in adult male mice.

Astrocyte modulation of extinction impairments in ethanol-dependent female mice.

Rates of alcohol use disorders are increasing in women, and there is growing evidence that both the cognitive and biological consequences of alcohol dependence are distinct in women as compared to men. Despite this, the neurobehavioral outcomes of chronic alcohol exposure are poorly characterized in women and female animals. In this study, we find that ethanol dependence impaired extinction of reward seeking in a food conditioned place preference task in female mice. At the same time point, ethanol-dependent females exhibited astrocytic dysregulation as indicated by a brain region-specific reduction in glial fibrillary acidic protein (GFAP) expression. Using a chemogenetic strategy, we demonstrate that modulating astrocyte function via chemogenetic activation of Gq-signaling in nucleus accumbens astrocytes transiently rescued extinction in ethanol-dependent females without impacting basal reward seeking. These findings identify astrocyte function as a potential target for the restoration of behavioral flexibility following chronic alcohol exposure in females.