title: Lorcaserin Suppresses Oxycodone Self-Administration and Relapse Vulnerability in Rats.
abstract: Opioid use disorder (OUD) is a major public health problem. High relapse rates and poor treatment retention continue to pose major challenges in OUD treatment. Of the abused opioids, oxycodone is well described to maintain self-administration and evoke the durable conditioned responses ("cue reactivity") that result from pairing of opioid-related stimuli (e.g., paraphernalia) with repeated abuse. Serotonin (5-HT) neurotransmission, particularly through the 5-HT2Creceptor (5-HT2CR), regulates psychostimulant reward and cue reactivity, and in the present experiments, we investigated the hypothesis that the selective 5-HT2CR agonist lorcaserin, which is approved by the United States Food and Drug Administration (FDA) for the treatment of obesity, will suppress oxycodone self-administration and oxycodone-associated cue reactivity in rats. We found that lorcaserin inhibited oxycodone intake, an effect blocked by the selective 5-HT2CR antagonist SB242084. Lorcaserin also decreased responding for the discrete cue complex ("cue reactivity") previously associated with delivery of oxycodone (i.e., stimulus lights, infusion pump sounds) in both abstinence and extinction-reinstatement models. The selected dose range of lorcaserin (0.25-1 mg/kg) does not overtly alter spontaneous behaviors nor operant responding on inactive levers in the present study. Taken together, the ability of lorcaserin to reduce the oxycodone self-administration and decrease cue reactivity associated with relapse highlights the therapeutic potential for lorcaserin in the treatment of OUD.
authors.affiliation: Center for Addiction Research and Department of Pharmacology and Toxicology, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Harshini
authors.initials: H
authors.lastname: Neelakantan
authors.affiliation: Center for Addiction Research and Department of Pharmacology and Toxicology, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Erica D
authors.identifier: 0000-0002-5502-0610
authors.initials: ED
authors.lastname: Holliday
authors.affiliation: Center for Addiction Research and Department of Pharmacology and Toxicology, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Fox
authors.affiliation: Center for Addiction Research and Department of Pharmacology and Toxicology, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Sonja J
authors.initials: SJ
authors.lastname: Stutz
authors.affiliation: New York State Psychiatric Institute Division on Substance Use Disorders, Columbia University , New York, New York 10032, United States.
authors.forename: Sandra D
authors.initials: SD
authors.lastname: Comer
authors.affiliation: New York State Psychiatric Institute Division on Substance Use Disorders, Columbia University , New York, New York 10032, United States.
authors.forename: Margaret
authors.initials: M
authors.lastname: Haney
authors.affiliation: Center for Addiction Research and Department of Pharmacology and Toxicology, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Noelle C
authors.initials: NC
authors.lastname: Anastasio
authors.affiliation: Institute for Drug and Alcohol Studies and Department of Psychiatry, Virginia Commonwealth University , Richmond, Virginia 23219, United States.
authors.forename: F Gerard
authors.initials: FG
authors.lastname: Moeller
authors.affiliation: Center for Addiction Research and Department of Pharmacology and Toxicology, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Kathryn A
authors.identifier: 0000-0002-4257-1739
authors.initials: KA
authors.lastname: Cunningham
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009293:Opioid-Related Disorders; D010098:Oxycodone / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D012646:Self Administration; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology
chemical_list: C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D001552:Benzazepines; D007211:Indoles; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; C506658:lorcaserin; D010098:Oxycodone
keywords: 5-HT2C receptor; cue reactivity; lorcaserin; opioid; oxycodone; self-administration