Pharmacological studies of the acute effects of (+)-3,4-methylenedioxymethamphetamine on locomotor activity: role of 5-HT(1B/1D) and 5-HT(2) receptors.
The role of serotonin 5-HT(2) receptors (5-HT(2)R) 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-HT(2B/2C)R antagonist SB 206553 (1.0, 2.0, and 4.0 mg/kg). Administration of the 5-HT(1B/1D)R antagonist GR 127935 (2.5 mg/kg) or the 5-HT(2A)R 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-HT(2C)R exerts a strong inhibitory influence on the hyperactivity induced by (+)-MDMA, and that 5-HT(2C)R blockade unmasks hyperactivity mediated through several mechanisms.
Bankson
Michael G
MG
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555-1031, USA.
Cunningham
Kathryn A
KA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005464:Fluorobenzenes / Q000494:pharmacology; D006213:Hallucinogens / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D005464:Fluorobenzenes; D006213:Hallucinogens; D007211:Indoles; D010069:Oxadiazoles; D010879:Piperazines; D010880:Piperidines; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C090701:GR 127935; C094868:SB 206553; C079049:volinanserin; D018817:N-Methyl-3,4-methylenedioxyamphetamine