Research Paper
Subject Category: Neuropharmacology
British Journal of Pharmacology (2008) 153, 591–597; doi:10.1038/sj.bjp.0707590; published online 26 November 2007
Role of 
1-adrenoceptor subtypes in the effects of methylenedioxy methamphetamine (MDMA) on body temperature in the mouse
1Department of Physiology, Royal College of Surgeons in Ireland, Dublin, Ireland
Correspondence: Professor J Docherty, Department of Physiology, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. E-mail: docherty@rcsi.ie
Received 14 August 2007; Accepted 18 October 2007; Published online 26 November 2007.
Abstract
Background and purpose:
We have investigated the ability of 
1-adrenoceptor antagonists to affect the hyperthermia produced by methylenedioxy methamphetamine (MDMA) in conscious mice.
Experimental approach:
Mice were implanted with temperature probes under ether anaesthesia and allowed 2 weeks recovery. MDMA (20 mg kg-1) was administered subcutaneously 30 min after vehicle or test antagonist or combination of antagonists and effects on body temperature monitored.
Key results:
Following vehicle, MDMA produced a hyperthermia, reaching a maximum increase of 1.8 °C at 140 min. Prazosin (0.1 mg kg-1) revealed an early significant hypothermia to MDMA of -1.94 °C. The 1A-adrenoceptor antagonist RS 100329 (0.1 mg kg-1), or the 1D-adrenoceptor antagonist BMY 7378 (0.5 mg kg-1) given alone, did not reveal a hypothermia to MDMA, but the combination of the two antagonists revealed a significant hypothermia to MDMA. The putative 1B-adrenoceptor anatagonist cyclazosin (1 mg kg-1) also revealed a significant hypothermia to MDMA, but actions of cyclazosin at the other 1-adrenoceptor subtypes cannot be excluded.
Conclusions and implications:
More than one subtype of 1-adrenoceptor is involved in a component of the hyperthermic response to MDMA in mouse, probably both 1A- and 1D-adrenoceptors, and removal of this 1-adrenoceptor-mediated component reveals an initial hypothermia.
Keywords:
MDMA, hyperthermia, 1-adrenoceptor, 1A-adrenoceptor, 1D-adrenoceptor
Abbreviations:
BMY 7378, (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4.5) decane-7,9-dione; MDMA, methylenedioxy methamphetamine; RS 100329, 5-methyl-3-(3-(4-(2-(2,2,2,-trifluoroethoxy)phenyl)-1-piperazinyl)propyl)-2,4-(1H)-pyrimidinedione; WT, wild type
