Prevention of risperidone on MDMA((+)-3,4-methylenedioxymethamphetamine)-induced rise in core body temperature in rats and role of the serotonin 5-HT_<2A> receptor in the hyperthermic effects of MDMA

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MDMA (3,4-methylenidioxymetanphtamine) is a recreational drug that has become increasingly popular in Western countries. The use of MDMA by young people has increased in Japan. Life-threatening hyperthermia occurs with MDMA overdose. Since MDMA produces the acute and massive release of 5HT and DA from nerve endings, it is sometimes assumed that MDMA-induced hyperthermia is a consequence of 5HT and DA release and the subsequent stimulation of 5HT and DA receptors involved in thermoregulation. Considering these hypotheses, we investigated whether MDMA-induced hyperthermia is attenuated by risperidone, a potent DA and 5HT_2 receptor antagonist in rats. Risperidone 0.5mg/kg (other antagonists) or saline was intraperitoneally injected 15min prior to the subcutaneous administration of MDMA 10mg/kg, and rectal temperature was measured every 30min. MDMA induced an acute and strong increase in rectal temperature, but the increase in rectal temperature was significantly attenuated by pretreatment with risperidone from 30min until 120min after MDMA administration. The D_1 receptor antagonist SCH23390 attenuated MDMA-induced hyperthermia, but the D_2 receptor antagonist L-741626 failed to attenuate the hyperthermia. The 5TH_<1A> receptor antagonist WAY 100635 did not attenuate MDMA-induced hyperthermia. 5HT_<2A> receptor antagonist ritanserine attenuated the hyperthermia. The 5HT_<2C> antagonist SB242084 and 5HT_<2B/2C> antagonist SB206553 did not attenuate MDMA-induced hyperthermia. These results suggest that risperidone attenuated MDMA-induced hyperthermia due to D_1 and 5HT_<2A> receptor antagonist action, and that risperidone may be useful for the treatment of MDMA-induced hyperthermia.