Investigating the Effects of Early Life Stress and Alcohol Exposure on BNST Activation: Social Behavior Analysis in Mice

Alcohol Use Disorder (AUD) impacts over 10% of people aged 12+ in the United States. Childhood trauma has been identified as a leading risk factor for the development of substance use disorders, of which AUD is the most common. AUD not only has lasting impacts on physical health, but is a major detriment to mental health and often results in the development of antisocial behavior. The underpinning neural connection between childhood trauma, alcohol use, and social behavior is not fully known. However, all three have been independently traced back to the same brain region, the bed nucleus stria terminalis (BNST). The BNST plays a key role in social threat recognition and reward seeking. In mouse models, Early Life Stress (ELS) elicits increased activity in the BNST correlated with increased alcohol drinking. Additionally, changes in the BNST related to alcohol use and stress have separately been shown to impact social behavior trends. By analyzing the impact of ELS and chronic alcohol exposure on sociability in mice, this research shows that the independent and combined effects of stress and alcohol are sex-specific, with females demonstrating significant decrease in social behavior. Additionally, analysis of cFos expression (a marker of elevated neuronal activity) suggests that alcohol exposure may increase social interaction-induced BNST activity in control subjects, but may decrease activity in ELS subjects. By determining the neural effects of ELS and chronic alcohol exposure on the BNST, more specific therapies can be developed to target this overlap in stimulus-based neuroplasticity. Increased understanding of the neural mechanisms behind drug-seeking behaviors and subsequent social deficits is key to advancing neuropsychiatric treatments for alcohol use disorder, and substance use disorders at large.