Abstract
The role of serotonin 5-HT2 receptors (5-HT2R) in the hyperactivity induced by (+)-3,4-methylenedioxy-methamphetamine ((+)-MDMA; 3 mg/kg) was investigated. Hyperactivity induced by (+)-MDMA was robustly potentiated by the 5-HT2B/2CR antagonist SB 206553 (1.0, 2.0, and 4.0 mg/kg). Administration of the 5-HT1B/1DR antagonist GR 127935 (2.5 mg/kg) or the 5-HT2AR antagonist M100907 (1.0 mg/kg) partially suppressed the potentiated hyperactivity seen following SB 206553 plus (+)-MDMA; a blockade to activity levels seen with (+)-MDMA alone was observed following the combination of GR 127935 plus M100907. A modest potentiative interaction was seen when SB 206553 was combined with the DA releaser amphetamine (0.5 mg/kg) or amphetamine plus the 5-HT releaser fenfluramine (4.0 mg/kg). SB 206553 (1–4 mg/kg), GR 127935 (2.5 mg/kg) and M100907 (1 mg/kg) did not alter spontaneous activity upon administration singly or in combination. These data suggest that activation of 5-HT2CR exerts a strong inhibitory influence on the hyperactivity induced by (+)-MDMA, and that 5-HT2CR blockade unmasks hyperactivity mediated through several mechanisms.
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Acknowledgements
We would like to thank Billy Doyon for his technical assistance in completing this work. The research was supported by the National Institute on Drug Abuse grants DA 006511, DA 00260 and DA 07287. This manuscript was presented by M.G.B. in partial fulfillment of the requirements for the Ph.D. degree to the Graduate School of Biomedical Sciences at the University of Texas Medical Branch. Portions of this work were presented at the annual meeting of The College on Problems of Drug Dependence held in San Juan, Puerto Rico, in June, 2000.
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Bankson, M., Cunningham, K. Pharmacological Studies of the Acute Effects of (+)-3,4-Methylenedioxymethamphetamine on Locomotor Activity: Role of 5-HT1B/1D and 5-HT2 Receptors. Neuropsychopharmacol 26, 40–52 (2002). https://doi.org/10.1016/S0893-133X(01)00345-1
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DOI: https://doi.org/10.1016/S0893-133X(01)00345-1
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