The Serotonin 2C Receptor Agonist Lorcaserin Attenuates Intracranial Self-Stimulation and Blocks the Reward-Enhancing Effects of Nicotine

ACS Chemical Neuroscience
Fiona D ZeebPaul J Fletcher

Abstract

Lorcaserin, a serotonin (5-hydroxytryptamine, 5-HT) 2C receptor agonist, was recently approved for the treatment of obesity. We previously suggested that 5-HT2C receptor agonists affect reward processes and reduce the rewarding effects of drugs of abuse. Here, we determined whether lorcaserin (1) decreases responding for brain stimulation reward (BSR) and (2) prevents nicotine from enhancing the efficacy of BSR. Rats were trained on the intracranial self-stimulation (ICSS) paradigm to nosepoke for BSR of either the dorsal raphé nucleus or left medial forebrain bundle. In Experiment 1, lorcaserin (0.3-1.0 mg/kg) dose-dependently reduced the efficacy of BSR. This effect was blocked by prior administration of the 5-HT2C receptor antagonist SB242084. In Experiment 2, separate groups of rats received saline or nicotine (0.4 mg/kg) for eight sessions prior to testing. Although thresholds were unaltered in saline-treated rats, nicotine reduced reward thresholds. An injection of lorcaserin (0.3 mg/kg) prior to nicotine prevented the reward-enhancing effect of nicotine across multiple test sessions. These results demonstrated that lorcaserin reduces the rewarding value of BSR and also prevents nicotine from facilitating ICSS. Hence, lor...Continue Reading

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Citations

Dec 26, 2015·Pharmacology, Biochemistry, and Behavior·Scott A BriggsEdward D Levin
Apr 15, 2015·ACS Chemical Neuroscience·Guy A Higgins, Paul J Fletcher
Apr 30, 2016·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Caleb J Browne, Paul J Fletcher
Jul 20, 2017·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Caleb J BrowneColin Harvey-Lewis
Oct 27, 2017·Journal of Psychopharmacology·Guy A HigginsPaul J Fletcher
Nov 7, 2019·Expert Opinion on Pharmacotherapy·Beverly G TchangAlpana P Shukla
Mar 27, 2018·Biophysical Reports·Yao PengZhi-Jie Liu
Dec 17, 2017·Neuropharmacology·Gregory T CollinsCharles P France

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