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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

利培酮对MDMA(()-3,4-亚甲二氧基甲基苯丙胺)引起的大鼠核心体温升高的预防作用以及血清素5-HT_<2A>受体在MDMA热效应中的作用

基本信息

批准号：
16591157
负责人：
NISHIJIMA Kohichi
金额：
$ 2.37万
依托单位：
JICHI MEDICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

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.

MDMA（3，4-亚甲二氧基间苯二甲胺）是一种娱乐性药物，在西方国家越来越受欢迎。在日本，年轻人使用摇头丸的情况有所增加。MDMA过量会发生危及生命的高热。由于MDMA产生急性和大量的5-HT和DA从神经末梢释放，有时认为MDMA诱导的体温过高是5-HT和DA释放和随后刺激参与体温调节的5-HT和DA受体的结果。考虑到这些假设，我们研究了MDMA诱导的大鼠体温升高是否被有效的DA和5HT_2受体拮抗剂利培酮减弱。在皮下注射MDMA 10 mg/kg前15 min腹腔注射利培酮0.5mg/kg（其他拮抗剂）或生理盐水，每30 min测量一次直肠温度。MDMA引起直肠温度的急性和强烈的增加，但在MDMA给药后30分钟至120分钟，利培酮预处理可显著减弱直肠温度的升高。D_1受体拮抗剂SCH 23390可减弱MDMA引起的体温升高，而D_2受体拮抗剂L-741626则不能减弱MDMA引起的体温升高。5TH_<1A>受体拮抗剂WAY 100635对MDMA诱导的体温升高无抑制作用。5-HT_2<2A>受体拮抗剂利坦丝氨酸可减轻体温升高。5-HT_<2C>（2B/2C）拮抗剂SB 242084和SB 206553对MDMA诱导的体温升高无拮抗作用。这些结果提示利培酮可能通过D_1和5HT_2受体拮抗剂的作用而减轻MDMA所致的体温升高<2A>，利培酮可能对MDMA所致的体温升高有治疗作用。