Hypothalamic-Pituitary-Thyroid axis and Sympathetic Nervous System involvement in the hyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)
by
Sprague JE, Banks ML, Cook VJ, Mills EM.
J Pharmacol Exp Ther 2003 Jan 21


ABSTRACT

An acute and potentially life-threatening complication associated with the recreational use of the 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) is hyperthermia. In the present study, Sprague-Dawley rats treated with MDMA (40 mg/kg, sc) responded with a significant increase (maximal at 1 hr) in rectal and skeletal muscle temperatures that lasted for at least three hours post treatment. Hypophysectomized (HYPO) and thyroparathyroidectomized (TX) animals treated with MDMA (40 mg/kg, sc) did not become hyperthermic and in fact displayed a significant hypothermia. The HYPO and TX animals were also resistant to the serotonergic neurotoxic effects of MDMA assessed by serotonin measurements four to seven days later in the striatum and hippocampus. MDMA (40 mg/kg, sc) induced a significant increase in thyroxine levels one-hour post treatment. Thyroid hormone replacement in TX animals returned the hyperthermic response seen following MDMA. Prazosin, an alpha1-antagonist, (0.2 mg/kg, ip) administered thirty minutes before MDMA significantly attenuated the MDMA-induced increase in rectal temperature, but had no effect on skeletal muscle temperature. Cyanopindolol, a beta3-antagonist, (4 mg/kg, sc) administered thirty minutes before MDMA (40 mg/kg, sc) significantly attenuated the increase in skeletal muscle temperature, but had no effect on the rise in rectal temperature. The combination of prazosin and cyanopindolol resulted in an abolishment of MDMA-induced hyperthermia. The mechanisms of thermogenesis induced by MDMA appear to result from an interaction between the hypothalamic-pituitary-thyroid axis and the sympathetic nervous system, wherein mechanisms leading to core and skeletal muscle hyperthermia following MDMA exposure appear to be differentially regulated by alpha1 and beta3 adrenergic receptors.

Carvedilol
Metabolites
Prozac and ecstasy
Protect and survive
L-deprenyl and ecstasy
MDMA-induced hyperthermia
MDMA and body temperature
MDMA-induced hyperthermia in rhesus monkeys


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