Diferenças sexuais na resposta ao binge drinking em Zebrafish (Danio rerio)

Abstract

Alcohol consumption is a widespread behavior with deep historical roots in human societies. Despite its adverse health effects, its legality and social appeal contribute to its widespread use, particularly in abusive patterns such as binge drinking. This pattern is associated with numerous negative consequences, including cognitive, behavioral, and physiological impairments, as well as social and psychological risks. The effects of alcohol vary depending on the biological system affected, with the liver and central nervous system being the most impacted. Sex-based differences in alcohol responses, although acknowledged, remain underexplored. In this context, the zebrafish (Danio rerio) stands out as a robust experimental model for studying these differences. The species exhibits high genetic homology with humans, clear sexual dimorphism, and is widely used in neurobehavioral and toxicological research. The growing body of evidence for sex-specific responses to ethanol in zebrafish reinforces its value in investigating the biological basis of alcohol consumption and its consequences. In this study, we evaluated the behavioral and genetic responses of male and female zebrafish following acute exposure to high alcohol concentrations. Adult zebrafish were divided into control females (n = 27), females exposed to 1.5% alcohol (n = 24), control males (n = 27), and males exposed to 1.5% alcohol (n = 27). Alcohol exposure occurred for 20 minutes, once a week, over four weeks. Animals were assessed without alcohol in their system at the time of testing. Males exhibited increased anxiety-like behavior and decreased sociability, while both sexes showed heightened mirror reactivity in the aggression test following alcohol exposure. Gene expression analysis revealed that control males had higher expression of gaba1, drd2a, and th1 compared to control females. Alcohol altered the expression of gaba1, drd2a, tph1a, and th1, with males showing greater susceptibility to these changes. These findings highlight significant sex-dependent responses to binge drinking in zebrafish, emphasizing the importance of considering sex as a critical factor in alcohol research.