title: Characterization of the discriminative stimulus effects of lorcaserin in rats.
abstract: 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.
authors.affiliation: Departments of Pharmacology, University of Texas Health Science Center at San Antonio, TEXAS.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Serafine
authors.affiliation: 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.
authors.forename: Kenner C
authors.initials: KC
authors.lastname: Rice
authors.affiliation: Departments of Pharmacology, University of Texas Health Science Center at San Antonio, TEXAS. france@uthscsa.edu.|Departments of Psychiatry, University of Texas Health Science Center at San Antonio, TEXAS. france@uthscsa.edu.
authors.forename: Charles P
authors.initials: CP
authors.lastname: France
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D058826:Serotonin 5-HT2 Receptor Agonists; D012702:Serotonin Antagonists; C506658:lorcaserin
keywords: drug discrimination; lever press; lorcaserin; rat; serotonin receptor