Discriminative stimulus properties of (+/-)-fenfluramine: the role of 5-HT2 receptor subtypes.

Andrew C McCreary, Malgorzata Filip, Kathryn A Cunningham

Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555, USA.

Behavioral neuroscience 2003 Apr

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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-HT(2C/1B)R agonist mCPP and the 5-HT(2C)R agonist MK 212 fully substituted, whereas the 5-HT(2A/2C)R agonist DOI partially substituted, for the training drug. The 5-HT(2B)R agonist BW 723C86 engendered saline-lever responding. The 5-HT(2C/2B)R antagonist SB 206553 completely antagonized the fenfluramine discrimination a well as the full substitutions of mCPP and MK 212 and the partial substitution of DOI. The selective 5-HT(2A)R 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-HT(2C)R 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-HT(2C)R and to some extent by 5-HT(2A)R.

Citation

Andrew C McCreary, Malgorzata Filip, Kathryn A Cunningham. Discriminative stimulus properties of (+/-)-fenfluramine: the role of 5-HT2 receptor subtypes. Behavioral neuroscience. 2003 Apr;117(2):212-21