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Memantine attenuates 3,4-methylenedioxymethamphetamine-induced hyperthermia in rats
Koichi Nisijima1, Kyoko Kuboshima, Katsutoshi Shioda
1Department of Psychiatry, Jichi Medical University, Tochigi, Japan. midorin@jichi.ac.jp
Neuroscience Letters
|November 13, 2012
Summary
Memantine effectively reduced dangerous body temperature increases caused by 3,4-Methylenedioxymethamphetamine (MDMA) in rats. This suggests memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, may treat MDMA-induced hyperthermia.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- 3,4-Methylenedioxymethamphetamine (MDMA) is an illicit substance known to cause life-threatening hyperthermia.
- Currently, no established pharmacological treatments exist for MDMA-induced hyperthermia.
Purpose of the Study:
- To investigate the efficacy of memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, in treating MDMA-induced hyperthermia in a rat model.
- To explore the potential mechanisms underlying memantine's effects, specifically its interaction with NMDA receptors and its impact on serotonin (5-HT) and dopamine (DA) levels.
Main Methods:
- Rats were administered MDMA (10 mg/kg) and subsequently treated with varying doses of memantine (10 or 20 mg/kg) or vehicle.
- Body temperature was monitored to assess the hyperthermic response.
- Microdialysis was employed to measure neurotransmitter levels (5-HT, DA) in the anterior hypothalamus following memantine and MDMA administration.
- The effects of other NMDA receptor antagonists (MK-801, CGS 19755) and an α-7 nicotinic acetylcholine receptor (nAChR) antagonist (methyllycaconitine) were also evaluated.
Main Results:
- Memantine administration, both before and after MDMA, significantly reduced peak body temperature in rats.
- Memantine pretreatment did not alter the MDMA-induced increase in hypothalamic serotonin or dopamine levels.
- Other NMDA receptor antagonists (MK-801, CGS 19755) effectively suppressed MDMA-induced hyperthermia, while the α-7 nAChR antagonist did not.
Conclusions:
- The findings suggest that memantine's ability to mitigate MDMA-induced hyperthermia is primarily mediated through its NMDA receptor antagonist properties.
- Memantine's therapeutic effect does not appear to be directly related to modulation of serotonin or dopamine systems in the anterior hypothalamus.
- Memantine shows potential as a therapeutic agent for managing MDMA-induced hyperthermia in humans.
