The role of adolescent social exclusion on the vulnerability to alcohol- and stress-related disorders

Adverse social experiences during adolescence can induce long-lasting neurobiological changes, influencing adult behaviors and vulnerability to alcohol- and stress-related disorders. The aim of this thesis was to investigate the long-term consequences of adolescent social exclusion on behavior and on neuronal circuits associated with alcohol use and stress disorders. In Project 1, male and female Wistar rats were exposed to a novel social exclusion paradigm during adolescence (P21–60). We developed an adapted social play arena consisting of a communal cage divided by a plexiglass wall. All rats were single- housed and assigned either to a social exclusion (EXC) group or a social interaction (INT) group. During three daily 1-h sessions, EXC rats were isolated on one side of the divider, while INT rats were placed in same-sex pairs on the opposite side. In adulthood, animals were assessed in a battery of anxiety- and alcohol-related behavioral tests, including alcohol self-administration, motivation for alcohol, and stress-induced relapse to alcohol seeking. Results revealed sex-specific effects of adolescent social stress: socially excluded males exhibited a marked reduction in relapse, whereas socially excluded females displayed increased pain sensitivity. Building on these findings, Project 2 examined how social context influences stress reactivity. Male Wistar rats exposed to either the exclusion paradigm or complete social isolation underwent a classical fear-conditioning procedure, in which an auditory cue was paired with a 0.8-mA foot-shock. No significant group differences in fear learning or expression were detected, however, substantial inter-individual variability was observed, suggesting a need for further investigations in order to address subtle modulations of fear processing. In Project 3, we investigated neuronal networks engaged by different social contexts. Brain tissue from animals previously exposed to the social paradigm was processed for c-Fos immunohistochemistry to generate a brain-wide map of neuronal activation patterns after exclusion or social interaction. Analyses revealed group- and sex- specific differences in c-Fos expression, highlighting several brain regions and networks warranting future mechanistic investigation. 3 Overall, this research strengthens the view that adolescent social experience exerts enduring influences on adult behavior with clear sex-dependent effects. Moreover, it identifies potential brain regions involved in mediating responses to social exclusion and social interaction.