Baclofen prevents MDMA-induced rise
in core body temperature in rats
Bexis S, Phillis BD, Ong J, White JM, Irvine RJ.
Department of Clinical & Experimental Pharmacology,
University of Adelaide, Adelaide,
SA 5005, Australia.
Drug Alcohol Depend. 2004 Apr 9;74(1):89-96
ABSTRACTA number of deaths have been attributed to severe hyperthermia resulting from the ingestion of 3,4-methylenedioxymethamphetamine (MDMA). The mechanisms underlying these events are unclear. In an attempt to further advance our understanding of these mechanism the present study investigated the effects of the selective GABA(A) agonist muscimol and the GABA(B) agonist baclofen on MDMA-induced responses in the rat. Baclofen at 1 and 3mg/kg and muscimol at 0.3 and 1mg/kg administered alone had no effect on heart rate, core body temperature or spontaneous locomotor activity as measured by radiotelemetry. MDMA at 15mg/kg produced a significant increase in heart rate, body temperature and locomotor activity [Formula: see text] which were unaffected by prior treatment with muscimol. In contrast, prior treatment with baclofen (3mg/kg) resulted in MDMA causing a sustained lowering of body temperature [Formula: see text], with no effect on heart rate and a small transient delay in the increase in locomotor activity. Baclofen pretreatment (3mg/kg) not only prolonged the time taken for animals to reach a core body temperature of 40 degrees C [Formula: see text], but also reduced the percentage of rats attaining a core body temperature of 40 degrees C. These data suggest that stimulation of GABA(B) receptors may provide a mechanism for the treatment of MDMA-induced hyperthermia.History
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