Characterization of the discriminative stimulus effects of lorcaserin in rats
- J Exp Anal Behav. 2016 Sep;106(2):107-16. doi: 10.1002/jeab.222.
- 1. Departments of Pharmacology, University of Texas Health Science Center at San Antonio, TEXAS.
- 2. Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland.
- 3. Departments of Pharmacology, University of Texas Health Science Center at San Antonio, TEXAS. [email protected].
- 4. Departments of Psychiatry, University of Texas Health Science Center at San Antonio, TEXAS. [email protected].
Lorcaserin is approved by the Food and Drug Administration for treating Obesity and is under consideration for treating substance use disorders; it has agonist properties at serotonin (5-HT)2C receptors and might also have agonist properties at other 5-HT Receptor subtypes. This study used drug discrimination to investigate the mechanism(s) of action of lorcaserin. Male Sprague-Dawley rats discriminated 0.56 mg/kg i.p. lorcaserin from saline while responding under a fixed-ratio 5 schedule for food. Lorcaserin (0.178-1.0 mg/kg) dose-dependently increased lorcaserin-lever responding. The 5-HT2C receptor agonist mCPP and the 5-HT2A receptor agonist DOM each occasioned greater than 90% lorcaserin-lever responding in seven of eight rats. The 5-HT1A receptor agonist 8-OH-DPAT occasioned greater than 90% lorcaserin-lever responding in four of seven rats. The 5-HT2C receptor selective antagonist SB 242084 attenuated lorcaserin-lever responding in all eight rats and the 5-HT2A receptor selective antagonist MDL 100907 attenuated lorcaserin-lever responding in six of seven rats. These results suggest that, in addition to agonist properties at 5-HT2C receptors, lorcaserin also has agonist properties at 5-HT2A and 5-HT1A receptors. Because some drugs with 5-HT2A receptor agonist properties are abused, it is important to fully characterize the behavioral effects of lorcaserin while considering its potential for treating substance use disorders.