Serotonin 5-HT_2C receptor activation suppresses binge intake and the reinforcing and motivational properties of high-fat food

Binge eating disorder (BED) is characterized by dysfunctional hedonic food intake and reward-related processes. Activation of the serotonin (5-HT) 5-HT_2C receptor (5-HT_2CR) suppresses both food intake and reward-related behaviors and is thus poised to regulate BED. This study assessed the effects of 5-HT_2CR activation via the selective 5-HT_2CR agonist WAY163909 on binge eating-related behaviors in adult male Sprague-Dawley rats. Low doses of WAY163909 (1.0, 2.0 mg/kg) suppressed high-fat food (HFF) binge intake, but not standard food non-binge intake. WAY163909 (1.0 mg/kg) also attenuated operant responding for self-administered HFF pellets on fixed and progressive ratio schedules of reinforcement, indicating that 5-HT_2CR activation suppresses the reinforcing and motivational properties of HFF, respectively. These findings suggest that activation of the 5-HT_2CR may be effective at suppressing binge eating in patients with BED via suppression of the reinforcing and motivational properties of HFF. This work supports future studies targeting the 5-HT_2CR in the treatment of BED.