The effects of mirtazapine and fluoxetine on hyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA) in rats.
Makiko Kasai, Katsutoshi Shioda, Koichi Nisijima, Tatsuki Yoshino, Tatsunori Iwamura, Satoshi Kato
Neuroscience Letters July 15, 2011 DOI: 10.1016/j.neulet.2011.05.024 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | MDMA Mirtazapine Fluoxetine WAY100635 |
| Dose | MDMA 10 mg/kg; mirtazapine 5 mg/kg; fluoxetine 10 mg/kg; WAY100635 1 mg/kg |
| Topics | MDMA |
| Key findings | Mirtazapine (5 mg/kg) given before or after MDMA significantly attenuated MDMA-induced hyperthermia (rectal temperature above 41°C after MDMA 10 mg/kg) in rats, an effect unchanged by the 5-HT(1A) antagonist WAY100635. Fluoxetine (10 mg/kg) attenuated hyperthermia only when given before MDMA, not after. The authors conclude mirtazapine is unlikely to induce fatal hyperthermia with MDMA and may be effective against it, likely by blocking 5-HT(2A) receptor activation. |
Abstract
The use of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") as a recreational drug has spread worldwide. Fatal hyperthermia is a likely side effect of using MDMA in combination with monoamine oxidase inhibitors. However, most antidepressants do not pose a high risk of developing hyperthermia when used in conjunction with MDMA. Mirtazapine is a novel antidepressant and a potent 5-HT(2A) receptor antagonist. It remains to be elucidated whether mirtazapine is unlikely to have life-threatening implications in combination with MDMA. In the present study, we evaluated whether mirtazapine and fluoxetine influence MDMA-induced hyperthermia in rats. The rectal temperature of the rats increased to above 41°C following an injection of MDMA (10mg/kg). Pre- and post-treatment administration of mirtazapine (5mg/kg) significantly attenuated MDMA-induced hyperthermia. Administration of WAY100635 (1mg/kg), a 5-HT(1A) receptor antagonist, did not influence the ability of mirtazapine to decrease hyperthermia induced by MDMA. Although pretreatment administration of fluoxetine (10mg/kg) significantly attenuated MDMA-induced hyperthermia, post-treatment administration of the same drug had no effect. The differences in body temperature between the groups post-treated mirtazapine and the groups post-treated fluoxetine may be due to differing mechanisms of action of the two antidepressants. The present study indicates that mirtazapine is unlikely to induce fatal hyperthermia when used with MDMA, and it may be rather effective against MDMA-induced hyperthermia. Considering our previous study demonstrating that potent 5-HT(2A) antagonists completely inhibit MDMA-induced hyperthermia, the findings of the present study suggest that mirtazapine inhibits MDMA-induced hyperthermia mainly by blocking the activation of 5-HT(2A) receptors.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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and 6 more in the library