Role of α 1-adrenoceptor subtypes in the effects of methylenedioxy methamphetamine (MDMA) on body temperature in the mouse

Abstract

Background and purpose: We have investigated the ability of α 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 α 1A-adrenoceptor antagonist RS 100329 (0.1 mg kg -1), or the α 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 α 1B- adrenoceptor anatagonist cyclazosin (1 mg kg -1) also revealed a significant hypothermia to MDMA, but actions of cyclazosin at the other α 1-adrenoceptor subtypes cannot be excluded. Conclusions and implications: More than one subtype of α 1-adrenoceptor is involved in a component of the hyperthermic response to MDMA in mouse, probably both α 1A- and α 1D-adrenoceptors, and removal of this α 1-adrenoceptor-mediated component reveals an initial hypothermia. © 2008 Nature Publishing Group All rights reserved.