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

David V. Herin, Shijing Liu, Thomas Ullrich, Kenner C. Rice, Kathryn Cunningham

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Rationale: Contradictory evidence exists regarding the role of the 5-HT2A receptor (5-HT2AR) in hyperactivity and hyperthermia elicited by the substituted amphetamine (+)-3,4- methylenedioxymethamphetamine. Objectives: The present studies examined the ability of the selective 5-HT2AR 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-HT2AR contributes to the generation of peripheral hyperactivity and rearing and, especially, the hyperthermia evoked by (+)-MDMA and that 5-HT2AR antagonists should be further investigated as treatments for the psychological and hyperthermic effects of (±)-MDMA.

Original languageEnglish (US)
Pages (from-to)505-513
Number of pages9
JournalPsychopharmacology
Volume178
Issue number4
DOIs
StatePublished - Apr 2005

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N-Methyl-3,4-methylenedioxyamphetamine
Receptor, Serotonin, 5-HT2A
Fever
Serotonin 5-HT2 Receptor Antagonists
Induced Hyperthermia
Amphetamine
MDL 100907

Keywords

  • Hyperactivity
  • Hyperthermia
  • M100907
  • MDMA

ASJC Scopus subject areas

  • Pharmacology

Cite this

Role of the serotonin 5-HT2A receptor in the hyperlocomotive and hyperthermic effects of (+)-3,4-methylenedioxymethamphetamine. / Herin, David V.; Liu, Shijing; Ullrich, Thomas; Rice, Kenner C.; Cunningham, Kathryn.

In: Psychopharmacology, Vol. 178, No. 4, 04.2005, p. 505-513.

Research output: Contribution to journalArticle

Herin, David V. ; Liu, Shijing ; Ullrich, Thomas ; Rice, Kenner C. ; Cunningham, Kathryn. / Role of the serotonin 5-HT2A receptor in the hyperlocomotive and hyperthermic effects of (+)-3,4-methylenedioxymethamphetamine. In: Psychopharmacology. 2005 ; Vol. 178, No. 4. pp. 505-513.
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