Role of alpha2A-adrenoceptors in the effects of MDMA on body temperature in the mouse.
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.
Bexis
Sotiria
S
Department of Physiology, Royal College of Surgeons in Ireland, Dublin.
Docherty
James R
JR
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced; D006213:Hallucinogens / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D018341:Receptors, Adrenergic, alpha-2 / Q000172:deficiency / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D006213:Hallucinogens; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D018341:Receptors, Adrenergic, alpha-2; D018490:Serotonin Agents; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D003000:Clonidine; C072125:BRL 44408