Sex differences in compulsive alcohol drinking phenotypes: implications for decision-making and social behavior in a preclinical model.

Rationale: Compulsivity is increasingly recognized as a transdiagnostic trait that amplifies vulnerability to alcohol use disorders. However, its specific role in shaping social behavior and decision-making remains underexplored.

Objective: This study aimed to identify a vulnerable phenotype characterized by compulsive alcohol drinking and evaluate its behavioral alterations within the social behavior and cognitive processes domains of the Research Domain Criteria (RDoC), considering sex as a modulatory factor.

Methods: Male and female Wistar rats were exposed to Schedule-Induced Polydipsia (SIP), first with water and then with alcohol. Distinct groups were formed based on intake patterns following a cluster-based analysis. We then assessed social subordination with the social dominance tube test (SDTT), sociability and social novelty with the three-chambered Crawley's test (3CT), and decision-making with the rodent Gambling Task (rGT).

Results: We identified four distinct behavioral profiles: Low Compulsive, Compulsive Alcohol, Compulsive Water, and High Compulsive. This segmentation revealed sex-specific distributions: males were overrepresented in high alcohol consumption clusters, while females were more prevalent in low-consumption profiles, indicating sex-related susceptibility. The High Compulsive phenotype diverged from the Compulsive Alcohol group, showing lower hierarchical status and a less risky decision-making strategy, whereas no significant differences were found in overall social interaction between groups. However, general alcohol consumption diminished general sociability and abolished sex differences, suggesting a disruption of innate social motivation.

Conclusions: These findings support that the combination of compulsivity and alcohol intake increases behavioral vulnerability, specifically in domains of social competence and decision-making.