risperidone supress cocaine-induced hyperthermia and dopamine level increasing in rat

可卡因是一种非法的精神兴奋剂，在全球广泛使用。热疗与可卡因致死性效应密切相关。据报道，可卡因主要通过引起DA的释放来诱导高热。我们假设利培酮可以抑制可卡因引起的高热。可卡因s.c.注射引起大鼠体温升高，注射利培酮可明显抑制大鼠体温升高。D1和5-HT2A受体拮抗剂可预防可卡因诱导的高温；因此，利培酮预防可卡因性高热的能力可能主要归因于其D1和5-HT2A受体的拮抗作用。在微透析研究中，我们发现可卡因ig可使下丘脑前部DA、5-HT和NA水平升高，利培酮预处理可显著抑制可卡因诱导的DA水平升高。我们的结果表明，利培酮是一种潜在的有用的药物，用于治疗人类可卡因引起的急性高热。

Cocaine, an illegal psychostimulant, is widely used globally. Hyperthermia is closely related to cocaine lethality effect. Cocaine has been reported to induce hyperthermia mainly by causing DA release. We hypothesized that risperidone could suppress cocaine-induced hyperthermia. Cocaine s.c. injection induced hyperthermia in rats, which was significantly suppressed by the injected risperidone. D1 and 5-HT2A receptor antagonists prevent cocaine-induced hyperthermia; thus,risperidone`s ability to prevent cocaine-induced hyperthermia might be mainly attributable to its D1 and 5-HT2A receptor antagonism.In the microdialysis study, we found that i.p. cocaine administration increased DA, 5-HT, and NA levels in the anterior hypothalamus, and that risperidone pretreatment significantly suppressed the cocaine-induced increase in DA levels.Our results indicate that risperidone is a potentially useful drug for treating cocaine-induced acute hyperthermia in humans.