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Effect of risperidone on acute methamphetamine-induced hyperthermia in rats.
Drug Alcohol Depend 2010; 111(3):241-9DA

Abstract

The abuse of methamphetamine (METH) is popular in many parts of the world. The number of fatal cases related to METH-induced hyperthermia is increasing, but no definitive therapy has yet been found. In the present study, we investigated the ability of risperidone to attenuate acute METH-induced hyperthermia and the mechanism of its action. When administered before and after a single high METH dose (10 mg/kg), risperidone significantly suppressed acute METH-induced hyperthermia in a dose-dependent manner. The same effect was produced by dopamine-1 (DA(1)) and serotonin-2A (5-HT(2A)) receptor blockers, but not by D₂, 5-HT(1A), 5-HT(2B/2C), or 5-HT(2C) receptor blockers, demonstrating that risperidone suppressed METH-induced hyperthermia by blocking the D(1) and 5-HT(2A) receptors. A microdialysis study showed that when METH (10 mg/kg) was subcutaneously injected into rats, the levels of DA, 5-HT, glutamate, and the nitric oxide (NO) metabolites NOx (NO₂⁻+ NO₃⁻) in the anterior hypothalamus increased. Risperidone pretreatment significantly attenuated increases in the levels of DA, 5-HT, glutamate, and NOx. The present study indicates that risperidone may be an effective drug for treating METH-induced hyperthermia in humans and that METH influences the DA and 5-HT neuron systems as well as other neuron systems, including the glutamate and NO systems.

Authors+Show Affiliations

Department of Psychiatry, Jichi Medical University, Tochigi, Japan. kazs@jichi.ac.jp

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20541333

Citation

Shioda, Katsutoshi, et al. "Effect of Risperidone On Acute Methamphetamine-induced Hyperthermia in Rats." Drug and Alcohol Dependence, vol. 111, no. 3, 2010, pp. 241-9.
Shioda K, Nisijima K, Yoshino T, et al. Effect of risperidone on acute methamphetamine-induced hyperthermia in rats. Drug Alcohol Depend. 2010;111(3):241-9.
Shioda, K., Nisijima, K., Yoshino, T., & Kato, S. (2010). Effect of risperidone on acute methamphetamine-induced hyperthermia in rats. Drug and Alcohol Dependence, 111(3), pp. 241-9. doi:10.1016/j.drugalcdep.2010.05.001.
Shioda K, et al. Effect of Risperidone On Acute Methamphetamine-induced Hyperthermia in Rats. Drug Alcohol Depend. 2010 Oct 1;111(3):241-9. PubMed PMID: 20541333.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of risperidone on acute methamphetamine-induced hyperthermia in rats. AU - Shioda,Katsutoshi, AU - Nisijima,Koichi, AU - Yoshino,Tatsuki, AU - Kato,Satoshi, Y1 - 2010/06/11/ PY - 2010/01/07/received PY - 2010/04/27/revised PY - 2010/05/03/accepted PY - 2010/6/15/entrez PY - 2010/6/15/pubmed PY - 2011/8/13/medline SP - 241 EP - 9 JF - Drug and alcohol dependence JO - Drug Alcohol Depend VL - 111 IS - 3 N2 - The abuse of methamphetamine (METH) is popular in many parts of the world. The number of fatal cases related to METH-induced hyperthermia is increasing, but no definitive therapy has yet been found. In the present study, we investigated the ability of risperidone to attenuate acute METH-induced hyperthermia and the mechanism of its action. When administered before and after a single high METH dose (10 mg/kg), risperidone significantly suppressed acute METH-induced hyperthermia in a dose-dependent manner. The same effect was produced by dopamine-1 (DA(1)) and serotonin-2A (5-HT(2A)) receptor blockers, but not by D₂, 5-HT(1A), 5-HT(2B/2C), or 5-HT(2C) receptor blockers, demonstrating that risperidone suppressed METH-induced hyperthermia by blocking the D(1) and 5-HT(2A) receptors. A microdialysis study showed that when METH (10 mg/kg) was subcutaneously injected into rats, the levels of DA, 5-HT, glutamate, and the nitric oxide (NO) metabolites NOx (NO₂⁻+ NO₃⁻) in the anterior hypothalamus increased. Risperidone pretreatment significantly attenuated increases in the levels of DA, 5-HT, glutamate, and NOx. The present study indicates that risperidone may be an effective drug for treating METH-induced hyperthermia in humans and that METH influences the DA and 5-HT neuron systems as well as other neuron systems, including the glutamate and NO systems. SN - 1879-0046 UR - https://www.unboundmedicine.com/medline/citation/20541333/Effect_of_risperidone_on_acute_methamphetamine_induced_hyperthermia_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0376-8716(10)00164-X DB - PRIME DP - Unbound Medicine ER -