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PRECLINICAL STUDY: Schedule‐induced alcohol drinking: non‐selective effects of acamprosate and naltrexone

Acamprosate and naltrexone are therapeutically effective drugs that promote abstinence and prevent drinking relapse among alcohol‐dependent patients, and dose‐dependently decrease alcohol self‐administration in animals. The purpose of this experiment was to investigate the behavioral specificity of acamprosate and naltrexone treatment in mice on alcohol drinking elicited in a schedule‐induced polydipsia (SIP) task. Food‐deprived male C57BL/6J (B6) mice were divided into three groups assigned to a 5% alcohol SIP, water SIP, or a 1‐hour limited access regulatory water drinking task. Injections (intraperitoneal) of acute (0, 50, 100, 200, 400 mg/kg) and chronic (2 × 100 mg/kg, 10 days) acamprosate, or naltrexone (0, 1.0, 2.5, 5.0 mg/kg) were administered. Behavioral drug specificity was determined by comparing alterations in alcohol or water consumption in SIP with alterations in limited access drinking. Additionally, drug effects on drinking‐specific measures (g/kg consumption and lick efficiency) were compared with those of non‐drinking measures (head entries for food and locomotor activity) during SIP. In comparison with saline injections, acute acamprosate (400 mg/kg) reduced both alcohol and water drinking in both SIP and the regulatory drinking conditions, but had no significant effects on non‐drinking measures. Chronic administration of acamprosate reduced both alcohol and water drinking during SIP, but did not significantly affect regulatory drinking or non‐drinking measures. Naltrexone (1.0, 2.5, 5.0 mg/kg) reduced alcohol and water drinking in both paradigms, and at the highest dose, significantly reduced head entries for food. These results indicate that acamprosate (acute and chronic) and naltrexone are relatively non‐selective in their effects on alcohol self‐administration in this task.