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

Colin Harvey-Lewis; Zhaoxia Li; Guy A Higgins; Paul J Fletcher

doi:10.1016/j.neuropharm.2015.09.028

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.

Authors

Colin Harvey-Lewis¹, Zhaoxia Li², Guy A Higgins³, Paul J Fletcher⁴

Affiliations

¹ Section of Biopsychology and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, M5T 1R8, Canada. Electronic address: colin.harvey-lewis@camh.ca.
² Section of Biopsychology and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, M5T 1R8, Canada.
³ InterVivo Solutions Inc., 120 Carlton St., Toronto, ON, M5A 4K2, Canada; Dept. Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada.
⁴ Section of Biopsychology and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, M5T 1R8, Canada; Dept. of Psychiatry, University of Toronto, Toronto, ON, Canada; Dept. of Psychology, University of Toronto, Toronto, ON, Canada.

PMID: 26427596
DOI: 10.1016/j.neuropharm.2015.09.028

Abstract

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*

Substances

Benzazepines
Dopamine Uptake Inhibitors
Serotonin Agents
lorcaserin
Cocaine

Grants and funding

MOP 13628/Canadian Institutes of Health Research/Canada