Role of the serotonin 5-HT2A receptor in the hyperlocomotive and hyperthermic effects of (+)-3,4-methylenedioxymethamphetamine.

Abstract

RATIONALE:

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.

OBJECTIVES:

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.

• Authors: David V Herin, Shijing Liu, Thomas Ullrich, Kenner C Rice, Kathryn A Cunningham
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 178 Issue 4 Pg. 505-13 (Apr 2005) ISSN: 0033-3158 [Print] Germany
• PMID: 15765263 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Fluorobenzenes
• Piperidines
• Receptor, Serotonin, 5-HT2A
• volinanserin
• N-Methyl-3,4-methylenedioxyamphetamine

Topics

• Animals
• Dose-Response Relationship, Drug
• Drug Antagonism
• Drug Therapy, Combination
• Fever (chemically induced, physiopathology)
• Fluorobenzenes (administration & dosage, pharmacokinetics)
• Injections, Intraperitoneal
• Injections, Subcutaneous
• Male
• Motor Activity (drug effects)
• N-Methyl-3,4-methylenedioxyamphetamine (administration & dosage, adverse effects, antagonists & inhibitors)
• Piperidines (administration & dosage, pharmacokinetics)
• Rats
• Rats, Sprague-Dawley
• Receptor, Serotonin, 5-HT2A (drug effects, physiology)
• Time Factors