EVALUATION OF ETHANOL ADMINISTRATION IN SWISS MICE AFTER CHRONIC ANTIANXIETY TREATMENT

Verma Prakash Bhanu*, Vishwakarma Sarandeep

Alcohol use disorder (AUD) is frequently associated with anxiety disorders, and the interaction between anxiolytic medications and ethanol consumption remains poorly understood. Clonazepam, a benzodiazepine that enhances γ-aminobutyric acid (GABA)-mediated neurotransmission, shares several neuropharmacological mechanisms with ethanol and may influence alcohol-seeking behavior. The present study investigated the effects of chronic clonazepam treatment on ethanol self-administration, ethanol intake, and anxiety-like behavior in Swiss albino mice. Male Swiss mice were trained to self-administer a 10% (w/v) ethanol solution using an operant conditioning paradigm. Following the establishment of stable baseline ethanol consumption, animals received clonazepam (0.5 mg/kg, i.p.) or vehicle according to the experimental protocol. Ethanol rewards, ethanol intake, water consumption, and total fluid intake were monitored throughout the study. Anxiety-like behavior was assessed using the Elevated Plus Maze (EPM), while locomotor activity was evaluated using an actophotometer. Blood ethanol concentrations were measured to validate ethanol self-administration behavior. Chronic clonazepam treatment significantly altered ethanol consumption patterns. Acute clonazepam exposure initially reduced ethanol self-administration and intake; however, prolonged treatment produced a significant increase in ethanol rewards, ethanol intake, and ethanol preference compared with baseline and vehicle-treated controls (p < 0.05). A significant positive correlation was observed between ethanol rewards and blood ethanol concentrations (p < 0.0001). In the EPM, clonazepam-treated mice spent significantly more time in the open arms and less time in the closed arms, indicating marked anxiolytic-like activity. No significant changes in locomotor activity were observed. These findings demonstrate that chronic clonazepam treatment exerts a biphasic effect on ethanol consumption while maintaining anxiolytic efficacy. Long-term benzodiazepine exposure may enhance alcohol-directed behaviors, highlighting potential implications for the management of anxiety disorders coexisting with alcohol use disorder.