Topiramate effects on ethanol and sucrose binge-like intake, anxiety- and compulsive-like behavior in non-dependent male and female C57BL/6J mice.

RATIONALE: Repetitive binge episodes are early-stage patterns in the addiction cycle associated with elevated anxiety and compulsive traits. Despite their high comorbidity and the growing off-label use of topiramate for binge-related disorders, its effects in non-dependent individuals remain poorly characterized and studies systematically comparing both sexes under identical experimental conditions remain scarce. OBJECTIVES: To evaluate the effects of topiramate on ethanol (EtOH) and sucrose binge-like intake, anxiety- and compulsive-like responses in non-dependent male and female C57BL/6J mice. METHODS: EtOH (20% v/v) and sucrose (10% w/v) binge-like intake were assessed in a standard Drinking in the Dark (DID) procedure following intraperitoneal topiramate (0, 30, or 60 mg/kg). Blood EtOH concentrations (BECs) were determined after EtOH DID. Anxiety-like and compulsive-like behaviors were assessed using the Elevated Plus Maze (EPM) and Marble Burying (MB) test. RESULTS: Topiramate significantly reduced EtOH binge-like intake at 60 mg/kg and BECs at 30 and 60 mg/kg, while males consumed more EtOH and showed higher BECs than females. Topiramate did not significantly alter sucrose binge-like intake, with females consuming less sucrose than males. Topiramate significantly reduced anxiety-like behavior in the EPM regardless of sex. In the MB test, the topiramate effect differed significantly across sexes, although these results most likely reflect a floor effect in vehicle-treated females. CONCLUSIONS: These findings provide preliminary evidence that topiramate reduces EtOH binge-like intake, anxiety- and compulsive-like behavior in non-dependent mice with a non-significant attenuation of sucrose binge-like intake. Further research is warranted to establish the translational relevance and to evaluate the preventive potential of topiramate in binge-related disorders.