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 °C ( P<0.001), but also reduced the percentage of rats attaining a core body temperature of 40 °C. These data suggest that stimulation of GABA B receptors may provide a mechanism for the treatment of MDMA-induced hyperthermia.