The Role of cAMP in Ecstasy-induced Hyperthermia
3, 4 methylenedioxymethamphetamine (MDMA, ecstasy) is a widely abused club drug that can mediate a potentially lethal hyperthermic response. MDMA induced stimulation of norepinephrine release leads to activation of mitochondrial uncoupling proteins (UCPs). UCPs generate heat through an increase in proton leak in the mitochondria, a process which is facilitated by free fatty acids (FFA). â3-adrenergic receptors (â3ARs) have been shown to regulate UCP activation. â3ARs are linked to adenylate cyclase and cAMP mediated intracellular changes. The aim of the present study was to define the role of cAMP in MDMA induced thermogenesis. When caffeine (15 mg/kg, ip), a non-selective inhibitor of phosphodiesterase, was administered 30 minutes before a non-thermogenic dose of MDMA (5 mg/kg, sc), hyperthermia developed. MDMA also mediated a rise in plasma FFA and a reduction in triglyceride levels. Forskolin (6.25 mg/kg, sc), an inducer of adenylate cyclase, also potentiated the hyperthermic effects of MDMA (5 or 40 mg/kg, sc). Whereas, pertussis toxin (30µg/kg, ip), an inhibitor of adenylate cyclase, attenuated the rise in core temperature. These findings suggest that cAMP plays a part in the augmentation of MDMA-induced hyperthermia.