Baclofen prevents MDMA-induced rise in core body temperature in rats

Abstract

A 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 3 mg/kg and muscimol at 0.3 and 1 mg/kg administered alone had no effect on heart rate, core body temperature or spontaneous locomotor activity as measured by radiotelemetry. MDMA at 15 mg/kg produced a significant increase in heart rate, body temperature and locomotor activity (P < 0.005) which were unaffected by prior treatment with muscimol. In contrast, prior treatment with baclofen (3 mg/kg) resulted in MDMA causing a sustained lowering of body temperature (P < 0.05), with no effect on heart rate and a small transient delay in the increase in locomotor activity. Baclofen pretreatment (3 mg/kg) not only prolonged the time taken for animals to reach a core body temperature of 40 degrees C (P < 0.001), 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.