Abstract

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.

Highlights

  • Alcohol use disorders (AUD) are common in the United States with a total lifetime prevalence of 30%1

  • This study investigated the influence of adolescent chronic variable social stress (CVSS) on adult binge-like ethanol consumption and anxiety- and depressive-like behaviors in inbred male and female C57BL/6J mice

  • Our results show that CVSS increased binge-like ethanol consumption in both male and female mice

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Summary

Introduction

Alcohol use disorders (AUD) are common in the United States with a total lifetime prevalence of 30%1. Adolescent social isolation, social instability, and repeated social defeat were found to increase voluntary ethanol consumption or self-administration in male rats and mice[9,10,11,12] These same adolescent social stress models elicited changes in anxiety/depression-like behaviors[4,10,13,14,15,16]. In adult male and female C57BL/6J mice, CVSS increased anxiety-like behavior on the elevated plus-maze (EPM) and evoked sex-specific alterations in synaptic excitability of prefrontal cortex (PFC) and nucleus accumbens (NAC) neurons in adult male and female C57BL/6J mice[19] These findings are intriguing because the development of anxiety-, depression-, and addiction-like behaviors is believed to involve synaptic modifications within the PFC and NAC among other corticolimbic regions[21]. Within individuals, greater levels of anxiety/depression-like behavior and lower levels of locomotor adaptation would be correlated with increased binge-like ethanol consumption

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