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 s.c.) responded with a significant increase (maximal at 1 h) in rectal and skeletal muscle temperatures that lasted for at least 3 h post-treatment. Hypophysectomized (HYPO) and thyroparathyroidectomized (TX) animals treated with MDMA (40 mg/kg s.c.) 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 4 to 7 days later in the striatum and hippocampus. MDMA (40 mg/kg s.c.) induced a significant increase in thyroxine levels 1 h post-treatment. Thyroid hormone replacement in TX animals returned the hyperthermic response seen after MDMA. Prazosin, an α1-antagonist (0.2 mg/kg i.p.), administered 30 min before MDMA significantly attenuated the MDMA-induced increase in rectal temperature, but had no effect on skeletal muscle temperature. Cyanopindolol, a β3-antagonist (4 mg/kg s.c.), administered 30 min before MDMA (40 mg/kg s.c.) 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 seem 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 after MDMA exposure seem to be differentially regulated by α1- and β3-adrenergic receptors.
Footnotes
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This research was sponsored by an Undergraduate Research Initiative Grant and funded by the Ohio Northern University College of Pharmacy.
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DOI: 10.1124/jpet.102.044982
- Abbreviations:
- MDMA
- 3,4-methylenedioxymethamphetamine
- SNS
- sympathetic nervous system
- UCP
- uncoupling proteins
- HPT
- hypothalamic-pituitary-thyroid
- HYPO
- hypophysectomized
- TX
- thyroparathyroidectomized
- 5-HT
- 5-hydroxytryptamine, serotonin
- T4
- thyroxine
- Received September 30, 2002.
- Accepted December 18, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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