Role of α2A‐adrenoceptors in the effects of MDMA on body temperature in the mouse

MDMA produces complex effects on body temperature, including both hypothermia and hyperthermia, depending on ambient temperature and species. This study in mice found that MDMA acts as an α₂-adrenoceptor agonist. The α₂-adrenoceptor agonist clonidine caused hypothermia in wild-type mice but not in mice lacking the α₂A-adrenoceptor. MDMA alone caused significant hyperthermia in wild-type mice, but a biphasic response (hypothermia followed by hyperthermia) in knockout mice. Blocking the α₂A-adrenoceptor in wild-type mice before MDMA resulted in initial hypothermia. Thus, MDMA's α₂A-adrenoceptor agonist actions surprisingly shift the body temperature response from biphasic to monophasic hyperthermia.

Study at a glance

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 α 2 ‐adrenoceptor agonist, and α 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 α 2A ‐knockout ( α 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 α 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 α 2 ‐KO mice. In WT mice, following the α 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, α 2 ‐adrenoceptor agonist actions of MDMA contribute to its effects on body temperature, but in a surprising way. Although selective α 2A ‐adrenoceptor agonism produces hypothermia, the α 2A ‐adrenoceptor actions of MDMA alter the body temperature response to MDMA from biphasic (hypothermia followed by hyperthermia) to monophasic hyperthemia. British Journal of Pharmacology (2005) 146 , 1–6. doi: 10.1038/sj.bjp.0706320