Role of alpha2A-adrenoceptors in the effects of MDMA on body temperature in the mouse.

Abstract

3,4-Methylenedioxymetamphetamine (MDMA) produces complex effects on body temperature, including hypo- and hyperthermic components that vary with ambient temperature and strain of rat. We have previously reported that MDMA is an alpha(2)-adrenoceptor agonist, and alpha(2)-adrenoceptor agonists such as clonidine produce hypothermia. The purpose of this study was to investigate the effects of MDMA on core body temperature measured by radiotelemetry in conscious wild-type (WT) and alpha(2A)-knockout (alpha(2A)-KO) mice. Clonidine (0.1 mg kg(-1), subcutaneously (s.c.)) produced a hypothermic response in WT mice, but did not significantly affect temperature in alpha(2)-KO mice. MDMA (20 mg kg(-1), s.c.) produced a significant hyperthermia in WT mice beginning at approximately 100 min after injection, recovering by 300 min, but produced a biphasic response, hypothermia followed by hyperthermia, in alpha(2)-KO mice. In WT mice, following the alpha(2A)-adrenoceptor antagonist 2-((4,5-dihydro-1H-imidazol-2-yl)methyl)-2,3-dihydro-1-methyl-1H-isoindole (1 mg kg(-1), s.c.), MDMA (20 mg kg(-1)) produced an initial hypothermia. Hence, alpha(2)-adrenoceptor agonist actions of MDMA contribute to its effects on body temperature, but in a surprising way. Although selective alpha(2A)-adrenoceptor agonism produces hypothermia, the alpha(2A)-adrenoceptor actions of MDMA alter the body temperature response to MDMA from biphasic (hypothermia followed by hyperthermia) to monophasic hyperthemia.

• Authors: Sotiria Bexis, James R Docherty
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 146 Issue 1 Pg. 1-6 (Sep 2005) ISSN: 0007-1188 [Print] England
• PMID: 16025144 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic Uptake Inhibitors
• Adrenergic alpha-Agonists
• Adrenergic alpha-Antagonists
• Hallucinogens
• Imidazoles
• Indoles
• Isoindoles
• Receptors, Adrenergic, alpha-2
• Serotonin Agents
• N-Methyl-3,4-methylenedioxyamphetamine
• Clonidine
• BRL 44408

Topics

• Adrenergic Uptake Inhibitors (pharmacology)
• Adrenergic alpha-Agonists (pharmacology)
• Adrenergic alpha-Antagonists (pharmacology)
• Animals
• Body Temperature (drug effects)
• Clonidine (pharmacology)
• Fever (chemically induced)
• Hallucinogens (pharmacology)
• Imidazoles (pharmacology)
• Indoles (pharmacology)
• Isoindoles
• Male
• Mice
• Mice, Knockout
• N-Methyl-3,4-methylenedioxyamphetamine (pharmacology)
• Receptors, Adrenergic, alpha-2 (deficiency, metabolism)
• Serotonin Agents (pharmacology)