Role of 5-HT2C receptors in effects of monoamine releasers on intracranial self-stimulation in rats

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• 作者：Clayton T. Bauer ; Matthew L. Banks ; Bruce E. Blough ; S. Stevens Negus
• 关键词：5 ; HT2C receptors ; Serotonin ; Dopamine ; Intracranial self ; stimulation ; Amphetamine ; Fenfluramine ; Methylenedioxymethamphetamine
• 刊名：Psychopharmacology
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：232
• 期：17
• 页码：3249-3258
• 全文大小：692 KB
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• 作者单位：Clayton T. Bauer (1)
  Matthew L. Banks (1)
  Bruce E. Blough (2)
  S. Stevens Negus (1)
  
  1. Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 N. 12th St., PO Box 980613, Richmond, VA, 23298, USA
  2. Center for Drug Discovery, Research Triangle Institute, Research Triangle Park, NC, USA
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Pharmacology and Toxicology
  Psychiatry
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-2072

文摘

Rationale Many monoamine releasers are abused by humans and produce abuse-related facilitation of intracranial self-stimulation (ICSS) in rats. Facilitation of ICSS in rats can be limited by monoamine releaser-induced serotonin (5-HT) release, but receptors that mediate 5-HT effects of monoamine releasers are unknown. Objectives The aim of this study is to investigate whether 5-HT2C receptor activation is necessary for rate-decreasing effects produced in an ICSS procedure in rats by the 5-HT-selective monoamine releaser fenfluramine and the non-selective releasers napthylisopropylamine (PAL-287) and (+)-3,4-methylenedioxymethamphetamine ((+)-MDMA). Methods Adult male Sprague-Dawley rats with electrodes implanted in the medial forebrain bundle were trained to lever press for brain stimulation under a “frequency-rate-ICSS procedure. Effectiveness of the 5-HT2C antagonist SB 242,084 was evaluated to block rate-decreasing effects produced by (1) the 5-HT2C agonist Ro 60-0175, (2) the 5-HT-selective releaser fenfluramine, and (3) the mixed-action dopamine (DA)/norepinephrine (NE)/5-HT releasers PAL-287 (1.0-.6?mg/kg) and (+)-MDMA (1.0-.2?mg/kg). For comparison, effectiveness of SB 242,084 to alter rate-decreasing effects of the kappa-opioid receptor agonist U69,593 and rate-increasing effects of the DA>5-HT releaser amphetamine was also examined. Results SB 242,084 pretreatment blocked rate-decreasing effects of Ro 60-0175 and fenfluramine, but not the rate-decreasing effects of U69,593 or the rate-increasing effects of amphetamine. SB 242,084 blunted the rate-decreasing effects and enhanced expression of rate-increasing effects of PAL-287 and (+)-MDMA. Conclusions These data suggest that 5-HT2C receptor activation contributes to rate-decreasing effects that are produced by selective and mixed-action 5-HT releasers in rats and that may oppose and limit the expression of abuse-related ICSS facilitation by these compounds.