Role of the serotonin 5-HT2A receptor in the hyperlocomotive and hyperthermic effects of (+)-3,4-methylenedioxymethamphetamine.
BACKGROUND
Contradictory evidence exists regarding the role of the 5-HT(2A) receptor (5-HT(2A)R) in hyperactivity and hyperthermia elicited by the substituted amphetamine (+)-3,4-methylenedioxymethamphetamine.


OBJECTIVE
The present studies examined the ability of the selective 5-HT(2A)R antagonist M100907 to block hyperactivity and hyperthermia produced across the (+)-MDMA dose-effect curve.


METHODS
Male rats were pretreated with M100907 (0, 0.25, 0.5, 1, and 2 mg/kg) followed by treatment with (+)-MDMA (0-12 mg/kg); activity was recorded for 90 min followed by determination of rectal temperature. Additionally, we investigated the ability of M100907 (0 and 0.5 mg/kg) to reverse hyperthermia elicited by (+)-MDMA (12 mg/kg).


RESULTS
The first study demonstrated that M100907 attenuated hyperactivity in the periphery of the monitor and eliminated rearing induced by (+)-MDMA (3 mg/kg) with no effect on basal activity. In two subsequent studies, (+)-MDMA (0-12 mg/kg) dose-dependently increased peripheral activity and rearing and produced hyperthermia. Pretreatment with M100907 decreased peripheral activity evoked by (+)-MDMA, right-shifted the dose-effect curve for rearing, and blocked (+)-MDMA-induced hyperthermia, while having no effect when administered alone. A final study demonstrated the ability of M100907 (0.5 mg/kg) to reverse hyperthermia produced by (+)-MDMA (12 mg/kg).


CONCLUSIONS
These results suggest that the 5-HT(2A)R contributes to the generation of peripheral hyperactivity and rearing and, especially, the hyperthermia evoked by (+)-MDMA and that 5-HT(2A)R antagonists should be further investigated as treatments for the psychological and hyperthermic effects of (+/-)-MDMA.
Herin
David V
DV
Department of Pharmacology and Toxicology, Center for Addiction Research, University of Texas Medical Branch, Galveston, TX 77555-1031, USA.
Liu
Shijing
S
Ullrich
Thomas
T
Rice
Kenner C
KC
Cunningham
Kathryn A
KA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D005334:Fever / Q000139:chemically induced* / Q000503:physiopathology; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000493:pharmacokinetics; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D005464:Fluorobenzenes; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; C079049:volinanserin; D018817:N-Methyl-3,4-methylenedioxyamphetamine