The 5-HT(2C) receptor agonist lorcaserin reduces cocaine self-administration, reinstatement of cocaine-seeking and cocaine induced locomotor activity

Neuropharmacology. 2016 Feb;101:237-45. doi: 10.1016/j.neuropharm.2015.09.028. Epub 2015 Sep 30.


Lorcaserin (Lorqess, Belviq(®)) is a selective 5-HT(2C) receptor agonist that has received FDA approval for the treatment of obesity. 5-HT(2C) receptor agonists are also efficacious in decreasing multiple aspects of cocaine motivation and reward in preclinical models. This would suggest that lorcaserin is a clinically available therapeutic with the potential to treat cocaine addiction. Here we report the effects of lorcaserin (0.1 mg/kg-1.0 mg/kg) on multiple aspects of cocaine-related behaviours in rats. We find that lorcaserin dose-dependently decreases cocaine self-administration on progressive and fixed ratio schedules of reinforcement. Lorcaserin also reduces reinstatement of cocaine-seeking behaviour in response to priming injections of cocaine and/or reintroduction of cocaine-associated cues. Finally, lorcaserin dose-dependently decreases cocaine-induced hyperlocomotion. Our results, when considered in concert with similar emergent findings in non-human primates, strongly support continued research into the potential of lorcaserin as a clinical treatment for cocaine addiction.

Keywords: 5-HT(2C) receptor; Cocaine; Locomotor activity; Lorcaserin; Reinstatement; Self-administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Benzazepines / pharmacology*
  • Cocaine / administration & dosage*
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / ethics
  • Dopamine Uptake Inhibitors / administration & dosage*
  • Dose-Response Relationship, Drug
  • Drug-Seeking Behavior / drug effects*
  • Extinction, Psychological / drug effects
  • Male
  • Motor Activity / drug effects*
  • Rats
  • Rats, Long-Evans
  • Reinforcement Schedule
  • Reinforcement, Psychology
  • Self Administration
  • Serotonin Agents / pharmacology*


  • Benzazepines
  • Dopamine Uptake Inhibitors
  • Serotonin Agents
  • lorcaserin
  • Cocaine