RESUMEN
Introduction: Adolescence is a critical period in cognitive and emotional development, characterized by high levels of social interaction and increases in risk-taking behavior including binge drinking. Adolescent exposure to social stress and binge ethanol have individually been associated with the development of social, emotional, and cognitive deficits, as well as increased risk for alcohol use disorder. Disruption of cortical development by early life social stress and/or binge drinking may partly underlie these enduring emotional, cognitive, and behavioral effects. The study goal is to implement a novel neighbor housing environment to identify the effects of adolescent neighbor housing and/or binge ethanol drinking on (1) a battery of emotional and cognitive tasks (2) adult ethanol drinking behavior, and (3) the nucleus accumbens and prefrontal cortex transcriptome. Methods: Adolescent male and female C57BL/6J mice were single or neighbor housed with or without access to intermittent ethanol. One cohort underwent behavioral testing during adulthood to determine social preference, expression of anxiety-like behavior, cognitive performance, and patterns of ethanol intake. The second cohort was sacrificed in late adolescence and brain tissue was used for transcriptomics analysis. Results: As adults, single housed mice displayed decreased social interaction, deficits in the novel object recognition task, and increased anxiety-like behavior, relative to neighbor-housed mice. There was no effect of housing condition on adolescent or adult ethanol consumption. Adolescent ethanol exposure did not alter adult ethanol intake. Transcriptomics analysis revealed that adolescent housing condition and ethanol exposure resulted in differential expression of genes related to synaptic plasticity in the nucleus accumbens and genes related to methylation, the extracellular matrix and inflammation in the prefrontal cortex. Discussion: The behavioral results indicate that social interaction during adolescence via the neighbor housing model may protect against emotional, social, and cognitive deficits. In addition, the transcriptomics results suggest that these behavioral alterations may be mediated in part by dysregulation of transcription in the frontal cortex or the nucleus accumbens.
RESUMEN
Adolescence is a critical developmental period characterized by enhanced social interactions, ongoing development of the frontal cortex and maturation of synaptic connections throughout the brain. Adolescents spend more time interacting with peers than any other age group and display heightened reward sensitivity, impulsivity and diminished inhibitory self-control, which contribute to increased risky behaviors, including the initiation and progression of alcohol use. Compared to adults, adolescents are less susceptible to the negative effects of ethanol, but are more susceptible to the negative effects of stress, particularly social stress. Juvenile exposure to social isolation or binge ethanol disrupts synaptic connections, dendritic spine morphology, and myelin remodeling in the frontal cortex. These structural effects may underlie the behavioral and cognitive deficits seen later in life, including social and memory deficits, increased anxiety-like behavior and risk for alcohol use disorders (AUD). Although the alcohol and social stress fields are actively investigating the mechanisms through which these effects occur, significant gaps in our understanding exist, particularly in the intersection of the two fields. This review will highlight the areas of convergence and divergence in the fields of adolescent social stress and ethanol exposure. We will focus on how ethanol exposure or social isolation stress can impact the development of the frontal cortex and lead to lasting behavioral changes in adulthood. We call attention to the need for more mechanistic studies and the inclusion of the evaluation of sex differences in these molecular, structural, and behavioral responses.