title: Lorcaserin, a selective 5-HT(2C) receptor agonist, decreases alcohol intake in female alcohol preferring rats.
abstract: Serotonergic systems in the brain have been found to be important in the addiction to alcohol. The purpose of this study was to evaluate the efficacy of a novel 5-HT2c receptor agonist, lorcaserin for reducing alcohol consumption in alcohol-preferring (P) rats. Adult female rats were allowed to drink water or alcohol (12%, v/v) using a standard two-bottle choice procedure. Once stable baselines were established, the acute (0, 0.3125, 0.625 and 1.25 mg/kg, s.c.), and chronic (0, 0.625 mg/kg, sc for 10 days) effects of lorcaserin on alcohol intake and preference were assessed at different time points. In a separate experiment, the effects of lorcaserin on locomotor activity were determined. Our results show that both 0.625 and 1.25 mg/kg lorcaserin significantly reduced alcohol intake at 2, 4 and 6 h. after the drug administration. The chronic administration of 0.625 mg/kg lorcaserin significantly reduced alcohol intake up to 6h every day after the injection and there was no sign of diminished efficacy of the drug during 10-day treatment. To determine the effects of lorcaserin on sucrose intake, rats were put on a two-bottle choice of water vs a solution of 7% sucrose. The high dose of lorcaserin (1.25 mg/kg, s.c.) reduced sucrose intake only for up to 2 h. When tested for locomotor activity, lorcaserin injected 20 min before testing significantly reduced locomotor activity at all doses. However, when it was injected 5.5h before the start of the 1-h session, neither dose had a significant effect on locomotor activity. These results show the efficacy of lorcaserin in reducing alcohol intake without a significant effect on water intake and locomotion suggesting the involvement of 5-HT2c receptors in alcohol seeking behavior. Further research is warranted to determine the possible efficacy of lorcaserin or similar drugs as treatments for the treatment of alcoholism.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA; Department of Psychology and Neuroscience, Duke University Medical Center, Durham, NC, USA. Electronic address: Azadi@duke.edu.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Rezvani
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA; Department of Psychology and Neuroscience, Duke University Medical Center, Durham, NC, USA.
authors.forename: Marty C
authors.initials: MC
authors.lastname: Cauley
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA; Department of Psychology and Neuroscience, Duke University Medical Center, Durham, NC, USA.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Levin
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D005260:Female; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology*
chemical_list: D001552:Benzazepines; D058826:Serotonin 5-HT2 Receptor Agonists; C506658:lorcaserin
keywords: Alcoholism; Drinking; Ethanol; Locomotor activity; Serotonin receptors; Sucrose