Effect of risperidone on acute methamphetamine-induced hyperthermia in rats

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 resent 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-HT2A) receptor blockers but not by D-2 5-HT1A 5-HT2B/2C or 5-HT2C receptor blockers demonstrating that risperidone suppressed METH-induced hyperthermia by blocking the D-1 and 5-HT2A 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 NO (NO2- + NO3-) in the anterior hypothalamus increased Risperidone pretreatment significantly attenuated increases in the levels of DA 5-HT glutamate and NO 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 (C) 2010 Elsevier Ireland Ltd All rights reserved