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

Sotiria Bexis, James R. Docherty

British Journal of Pharmacology July 18, 2005 DOI: 10.1038/sj.bjp.0706320 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Wild-type and α₂A-adrenoceptor knockout mice
Interventions MDMA Clonidine
Dose Clonidine 0.1 mg kg⁻¹, MDMA 20 mg kg⁻¹, antagonist 1 mg kg⁻¹
Duration 300 minutes post-injection
Topics MDMA
Keywords Hypothermia Hyperthermia Clonidine Thermoregulation Antagonist Pharmacology Endocrinology
Citations 43
Key findings MDMA's α₂A-adrenoceptor agonist actions alter the body temperature response from biphasic (hypothermia followed by hyperthermia) to monophasic hyperthermia in mice.

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

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

Study Year Design Participants
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) 1987 Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain 1987 Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells 2006 In vitro laboratory study
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Rats 1998 Experimental study
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Squirrel monkeys treated with MDMA 1999 Observational cohort

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MDMA Addiction Altered states of consciousness Philosophy of mind