The serotonin 2C receptor agonist lorcaserin, alone and in combination with the opioid receptor antagonist naltrexone, attenuates binge-like ethanol drinking.

The serotonin (5-HT) system has been implicated in the pathophysiology of alcohol (ethanol; EtOH) use disorders. Lorcaserin, a 5-HT2C receptor agonist, attenuates drug self-administration in animal models. We investigated the effects of lorcaserin on EtOH intake using the drinking-in-the-dark (DID) procedure, an animal model of binge-like drinking. We compared the effects of lorcaserin to those of the Food and Drug Administration (FDA)-approved drug naltrexone and examined the effects of combining lorcaserin and naltrexone. To examine whether effects were specific for EtOH, we examined the effects of lorcaserin and naltrexone, administered alone and in combination, on saccharin intake. Adult male C57BL/6J mice received EtOH access (20% v/v) for 2 h in the home-cage during the first 3 days of the DID procedure, beginning 3 h into the dark cycle. On day 4, mice were injected with lorcaserin, naltrexone, or a combination of lorcaserin and naltrexone prior to a 4-h EtOH access. Intake was measured at 2 and 4 h. Lorcaserin reduced EtOH intake in a dose-dependent fashion over the 2- and 4-h measurement periods. Naltrexone also reduced EtOH intake when administered alone, with dose-dependent effects being more pronounced over 2 h rather than the full 4-h session. Combining lorcaserin and naltrexone reduced binge-like EtOH drinking to a greater extent than either drug alone. A similar pattern of results was obtained for saccharin intake. These results suggest that lorcaserin and naltrexone can have additive effects on binge-like EtOH drinking. They also support continued research into the therapeutic potential of lorcaserin for alcohol use disorders.