The Serotonin Receptor Antagonists NAN-190, Methiothepin, Methysergide, Mianserin or Ondansetron Protect Against Methamphetamine-Induced Hyperthermia in Mice

The effect of some serotonin receptor antagonists was investigated on the body temperature ofmale mice. These antagonists produced significant reductions of body temperature in metha-mphetamine-induced hyperthermic male mice. Thus. the hyperthermia induced by metha-mphetamine(11mu mol/kg,i.p.) was antagonized by the previous i.p. administration of 1.06 mu mol/kg NAN- 190 (5-HT1A receptor antagonist), 22.1 mu mollkg methiothepin (5-HT1B/1D receptor antagonist), 2.13 mu mol/kg methyscrgide (5-HT 2A/2B receptor antagonist), 3.3 mu mol/kg mianscrin (5-HT2C and alpha 2 - adrenoceptor antagonist) or 0.003 mu mol/kg ondansetron (5-HT3 receptor antagonist). The present results indicate that central serotonin receptors may be involved in the hyperthermic effect of methamphetamine. Ondansetron, being effective at a relatively small dose (0.003 mu mol/kg) as compared to other antagonists used in this study, may be a potential antidote for methamphetamine-induced hyperthermia.