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Discriminative stimulus properties of (+/-)-fenfluramine: the role of 5-HT2 receptor subtypes.
Behav Neurosci. 2003 Apr; 117(2):212-21.BN

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.

Authors+Show Affiliations

McCreary AC
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555, USA.
Filip M
No affiliation info available
Cunningham KA
No affiliation info available

MeSH

AnimalsDiscrimination LearningDose-Response Relationship, DrugDrug CombinationsDrug InteractionsFenfluramineFluorobenzenesIndolesKetanserinMalePiperidinesPyrazinesPyridinesRatsReceptor, Serotonin, 5-HT2AReceptors, SerotoninReinforcement, PsychologySerotonin AntagonistsSerotonin Receptor AgonistsSpiro CompoundsSulfonamidesThiophenes

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12708517

Citation

McCreary, Andrew C., et al. "Discriminative Stimulus Properties of (+/-)-fenfluramine: the Role of 5-HT2 Receptor Subtypes." Behavioral Neuroscience, vol. 117, no. 2, 2003, pp. 212-21.
McCreary AC, Filip M, Cunningham KA. Discriminative stimulus properties of (+/-)-fenfluramine: the role of 5-HT2 receptor subtypes. Behav Neurosci. 2003;117(2):212-21.
McCreary, A. C., Filip, M., & Cunningham, K. A. (2003). Discriminative stimulus properties of (+/-)-fenfluramine: the role of 5-HT2 receptor subtypes. Behavioral Neuroscience, 117(2), 212-21.
McCreary AC, Filip M, Cunningham KA. Discriminative Stimulus Properties of (+/-)-fenfluramine: the Role of 5-HT2 Receptor Subtypes. Behav Neurosci. 2003;117(2):212-21. PubMed PMID: 12708517.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discriminative stimulus properties of (+/-)-fenfluramine: the role of 5-HT2 receptor subtypes. AU - McCreary,Andrew C, AU - Filip,Malgorzata, AU - Cunningham,Kathryn A, PY - 2003/4/24/pubmed PY - 2003/6/5/medline PY - 2003/4/24/entrez SP - 212 EP - 21 JF - Behavioral neuroscience JO - Behav Neurosci VL - 117 IS - 2 N2 - 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. SN - 0735-7044 UR - https://www.unboundmedicine.com/medline/citation/12708517/Discriminative_stimulus_properties_of__+/___fenfluramine:_the_role_of_5_HT2_receptor_subtypes_ DB - PRIME DP - Unbound Medicine ER -