Adolescent social stress increases anxiety-like behavior and ethanol consumption in adult male and female C57BL/6J mice.

Exposure to social stress is an important risk factor for comorbid affective disorders and problem alcohol use. To better understand mechanisms involved in social stress-induced affective disorder and alcohol use co-morbidity, we studied the effects of adolescent social stress on anxiety- and depression-like behaviors and binge-like ethanol consumption. Male and female C57BL/6J mice were exposed to chronic variable social stress (CVSS) or control conditions throughout adolescence (postnatal days, PND, 25-59) and then tested for anxiety-like behavior in the elevated plus maze and a novel open field environment, or depression-like behavior using the forced swim test on PND 64-66. Mice were then tested for binge-like ethanol consumption using the Drinking-in-the-Dark model. Male and female mice exposed to adolescent CVSS had increased adult anxiety-like behavior and increased locomotor adaptation to a novel environment. Further, CVSS mice consumed significantly more ethanol, but not saccharin, than controls. Despite group differences in both anxiety-like behavior and ethanol consumption, there was no relationship between these outcomes within individual mice. These data suggest that exposure to adolescent social stress is an important risk factor for later alcohol use and affective behaviors, but that social stress does not necessarily dictate co-morbidity of these outcomes.

Adolescent chronic variable social stress influences exploratory behavior and nicotine responses in male, but not female, BALB/cJ mice.

Anxiety disorders and nicotine use are significant contributors to global morbidity and mortality as independent and comorbid diseases. Early-life stress, potentially via stress-induced hypothalamic-pituitary-adrenal axis (HPA) dysregulation, can exacerbate both. However, little is known about the factors that predispose individuals to the development of both anxiety disorders and nicotine use. Here, we examined the relationship between anxiety-like behaviors and nicotine responses following adolescent stress. Adolescent male and female BALB/cJ mice were exposed to either chronic variable social stress (CVSS) or control conditions. CVSS consisted of repeated cycles of social isolation and social reorganization. In adulthood, anxiety-like behavior and social avoidance were measured using the elevated plus-maze (EPM) and social approach-avoidance test, respectively. Nicotine responses were assessed with acute effects on body temperature, corticosterone production, locomotor activity, and voluntary oral nicotine consumption. Adolescent stress had sex-dependent effects on nicotine responses and exploratory behavior, but did not affect anxiety-like behavior or social avoidance in males or females. Adult CVSS males exhibited less exploratory behavior, as indicated by reduced exploratory locomotion in the EPM and social approach-avoidance test, compared to controls. Adolescent stress did not affect nicotine-induced hypothermia in either sex, but CVSS males exhibited augmented nicotine-induced locomotion during late adolescence and voluntarily consumed less nicotine during adulthood. Stress effects on male nicotine-induced locomotion were associated with individual differences in exploratory locomotion in the EPM and social approach-avoidance test. Relative to controls, adult CVSS males and females also exhibited reduced corticosterone levels at baseline and adult male CVSS mice exhibited increased corticosterone levels following an acute nicotine injection. Results suggest that the altered nicotine responses observed in CVSS males may be associated with HPA dysregulation. Taken together, adolescent social stress influences later-life nicotine responses and exploratory behavior. However, there is little evidence of an association between nicotine responses and prototypical anxiety-like behavior or social avoidance in BALB/cJ mice.