Discriminative stimulus properties of (±)-fenfluramine: The role of 5-HT2 receptor subtypes

Andrew C. McCreary, Malgorzata Filip, Kathryn A. Cunningham

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The role of serotonin 5-HT2 receptors (5-HT2R) in the discriminative stimulus effects of fenfluramine was investigated. Male Sprague-Dawley rats were trained to discriminate (±)-fenfluramine (2 mg/kg ip) from saline using a 2-lever, water-reinforced paradigm. Drug-lever responding after fenfluramine was dose-dependent. The 5-HT2C/1B agonist mCPP and the 5-HT2CR agonist MK 212 fully substituted, whereas the 5-HT2A/2CR agonist DOI partially substituted, for the training drug. The 5-HT2BR agonist BW 723C86 engendered saline-lever responding. The 5-HT2C/2BR antagonist SB 206553 completely antagonized the fenfluramine discrimination as well as the full substitutions of mCPP and MK 212 and the partial substitution of DOI. The selective 5-HT2AR antagonist M100907 partially suppressed the stimulus effects of fenfluramine, mCPP, and MK 212 and almost fully attenuated the partial substitution of DOI. RS 102221, a selective 5-HT2CR antagonist that does not cross the blood-brain barrier, did not alter the fenfluramine cue. Results demonstrate that the discriminative stimulus effects of fenfluramine are centrally mediated by 5-HT2CR and to some extent by 5-HT2AR.

Original languageEnglish (US)
Pages (from-to)212-221
Number of pages10
JournalBehavioral neuroscience
Volume117
Issue number2
DOIs
StatePublished - Apr 1 2003

ASJC Scopus subject areas

  • Behavioral Neuroscience

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