Cocaine abuse and obesity are serious public health problems and studies suggest that both dopamine and serotonin (5-HT) systems are involved in regulating the consumption of drugs and food. Lorcaserin has 5-HT2C receptor agonist actions, is approved by the United States Food and Drug Administration for treating obesity, and might be effective for treating cocaine abuse. These studies characterized the pharmacokinetic and behavioral profiles of lorcaserin (intra-gastric administration; i.g.) and determined the effectiveness of lorcaserin to alter discriminative stimulus and reinforcing effects of cocaine (intravenous administration; i.v.) in rhesus monkeys. Administered acutely, lorcaserin dose dependently increased the occurrence of yawning while decreasing spontaneous activity and operant responding for food. These effects appeared within 30-60 min of administration and began to dissipate by 240 min, a time course closely matching plasma concentrations of lorcaserin. In monkeys discriminating cocaine from saline, lorcaserin alone did not occasion cocaine-appropriate responding but shifted the cocaine discrimination dose-response curve to the right and down in 2 of 3 monkeys Administered acutely, lorcaserin dose dependently decreased the rate at which monkeys responded for infusions of cocaine. When administered chronically, 3.2 mg/kg lorcaserin reduced the rate of cocaine-maintained responding by 50% for the duration of a 14-day treatment. Together, these results show that lorcaserin attenuates the discriminative stimulus and reinforcing effects of cocaine following acute and repeated administration, consistent with the view that it might have utility in treating cocaine abuse.
- The American Society for Pharmacology and Experimental Therapeutics