Risperidone attenuates and reverses hyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA) in rats.
Katsutoshi Shioda, Koichi Nisijima, Tatsuki Yoshino, Kyoko Kuboshima, Tatsunori Iwamura, Kunio Yui, Satoshi Kato
Neurotoxicology November 2008 DOI: 10.1016/j.neuro.2008.07.005 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Risperidone MDMA Ritanserin Ketanserin R-96544 WAY-100635 SB 206553 SB 242084 Haloperidol Sulpiride L-741626 SCH 23390 |
| Dose | MDMA (10 mg/kg) subcutaneously; risperidone (0.5 mg/kg) |
| Measures | body temperature, microdialysis |
| Topics | MDMA |
| Key findings | Risperidone dose-dependently suppressed MDMA-induced hyperthermia in rats, primarily via 5-HT2A receptor blockade and to a lesser extent D1 receptor blockade. It also inhibited MDMA-induced increases in hypothalamic dopamine and serotonin levels. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a widely used recreational drug. Despite an increase in the number of fatalities related to its use, no definite therapeutic method has been established thus far. In the present study, risperidone's ability to attenuate MDMA-induced hyperthermia and its mechanism of action were investigated in rats. The pharmacological effect of MDMA was evaluated using microdialysis. In the body temperature experiment, administration of risperidone before and after MDMA administration significantly suppressed MDMA-induced hyperthermia in a dose-dependent fashion. Furthermore, risperidone completely inhibited MDMA-induced hyperthermia at a low ambient temperature. Moreover, pretreatment with ritanserin, ketanserin, or R-96544, all of which are 5-HT(2A)-receptor antagonists, significantly prevented MDMA-induced hyperthermia. On the other hand, pretreatment with WAY-100635 (a 5-HT(1A) receptor antagonist), SB 206553 (a 5-HT(2B/2C) receptor antagonist), or SB 242084 (a 5-HT(2C) receptor antagonist) did not prevent MDMA-induced hyperthermia. Pretreatment with haloperidol, which blocks the dopamine (DA) receptors D(2) and D(1), significantly prevented MDMA-induced hyperthermia. However, sulpiride and L-741626, which are D(2) receptor blockers, did not prevent MDMA-induced hyperthermia. Pretreatment with SCH 23390 (a D(1) receptor antagonist) significantly prevented MDMA-induced hyperthermia. Furthermore, postadministration of ritanserin, haloperidol, and SCH23390 reversed MDMA-induced hyperthermia. These results demonstrate that the mechanism underlying the suppression of MDMA-induced hyperthermia by risperidone is primarily based on the drug's potent 5-HT(2A) receptor blocking effect, and to a lesser extent, on its D(1) receptor blocking effect. A microdialysis study showed that when MDMA (10mg/kg) was subcutaneously (s.c.) injected into the rats, the DA and serotonin (5-HT) levels in the anterior hypothalamus of the rats increased approximately 10- and 50-fold, respectively, as compared to their preadministration levels. These increases in the DA and 5-HT levels after MDMA injection were significantly suppressed by pretreatment with risperidone (0.5mg/kg). This suggested that both the DA and 5-HT systems were involved in the induction of hyperthermia by MDMA. Taken together, the present study's results indicate that risperidone may be an effective drug for the treatment of MDMA-induced hyperthermia in humans.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 21
- The role of monoamines in the changes in body temperature induced by 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives British Journal of Pharmacology March 3, 2010
- In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin2A Receptor Binding in 3,4-Methylenedioxymethamphetamine (MDMA or “Ecstasy”) and Hallucinogen Users Archives of General Psychiatry June 6, 2011
- Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in humans British Journal of Pharmacology March 8, 2012
- Role of Serotonin via 5-HT2B Receptors in the Reinforcing Effects of MDMA in Mice PLoS One November 20, 2009
- Differential effects of cathinone compounds andMDMAon body temperature in the rat, and pharmacological characterization of mephedrone‐induced hypothermia British Journal of Pharmacology October 8, 2012
and 16 more in the library
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- 5-HT2 receptors exert a state-dependent regulation of dopaminergic function: studies with MDL 100,907 and the amphetamine analogue, 3,4-methylenedioxymethamphetamine European Journal of Pharmacology November 1, 1992
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