Serotonin regulation of intermittent and continuous alcohol drinking in male and female C57BL/6J mice with systemic SB242084 and buspirone

This study aims to assess the therapeutic potentials of novel serotonergic compounds in treating alcohol use disorders by investigating the effects of SB242084 and buspirone on intermittent and continuous alcohol consumption in male and female mice. Adult male and female C57BL/6J mice were given two-bottle choice to 20% ethanol and water on an intermittent or continuous availability schedule. Drug testing consisted of intraperitoneal injections of 0.3, 1, 3 mg/kg SB242084 or 1, 3, 10 mg/kg buspirone, and subsequent alcohol and water consumption were measured. To monitor the drug effects on anxiety-like and locomotor behavior, the highest dose of each compound was administered before free activity in an open field. SB242084 dose-dependently attenuated alcohol drinking for intermittent alcohol drinking in male mice but did not significantly alter alcohol drinking in mice given continuous access. Two-hour and four-hour female drinking behavior was unaffected by SB242084. In comparison, buspirone not only suppressed intermittent and continuous alcohol drinking in both males and females but also reduced distance traveled in the open field test. Observed differences in responses to SB242084 between drinking groups may imply differing neural mechanisms between episodic and continuous drinking driven by serotonin. Reductions in drinking after buspirone treatment may be related to non-specific properties. These findings suggest the therapeutic potential of compounds blocking the 5-HT2C receptor for alcohol use disorders.