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

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McCreary AC, Filip M, Cunningham KA

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

Behav Neurosci. 2003 Apr;117(2):212-21.

PubMed ID

12708517 [ View in PubMed

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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-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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Fenfluramine	5-hydroxytryptamine receptor 2C	Protein	Humans	Yes	Agonist	Details