Characterization of the behavioral effects of lorcaserin in rats

Lorcaserin was recently approved by the FDA for the treatment of obesity, and its therapeutic effects are thought to be due to agonist activity at serotonin (5‐HT) 2C receptors. Lorcaserin also has affinity for other 5‐HT receptor subtypes, although its activity at those subtypes is not fully described. The current study examined the behavioral effects of lorcaserin (0.0032 – 32.0 mg/kg) in comparison to those of mCPP (0.032 – 1.0 mg/kg; 5‐HT 2C receptor agonist) and DOM (0.1 – 3.2 mg/kg; 5‐HT 2A receptor agonist) in 8 male Sprague Dawley rats. The behavioral profile of lorcaserin was similar to that of mCPP, in that both drugs dose‐dependently induced yawning and penile grooming. However, at some doses, lorcaserin (but not mCPP) also induced forepaw treading, an effect typically produced by 5‐HT 1A receptor agonists. In contrast, DOM dose‐dependently induced head twitching, back contractions, and hyperthermia. Pretreatment with lorcaserin (3.2 mg/kg), mCPP (3.2 mg/kg), or the 5‐HT 2A receptor selective antagonist MDL 100907 (0.01 mg/kg) attenuated DOM‐induced head twitching. Only lorcaserin significantly attenuated DOM‐induced hyperthermia. While the behavioral effects of lorcaserin are consistent with it having agonist activity at 5‐HT 2C receptors, these data suggest that it likely also has actions at 5‐HT 2A (e.g., antagonism) and 5‐HT 1A (e.g., agonism) receptors. A better understanding of the activity of lorcaserin at these receptor subtypes might facilitate its use for treating other disorders (e.g., drug abuse).