Psychopharmacology · 2025
Sex differences in compulsive alcohol drinking phenotypes: implications for decision-making and social behavior in a preclinical model.
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Olmedo-Córdoba Manuela, León José Juan, López-Villegas Álvaro, Martín-González Elena, Moreno-Montoya Margarita
Аннотация
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.
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.