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，在全球范围内广泛使用。高热与可卡因的致死作用密切相关。据报道，可卡因主要通过引起DA释放来诱导体温过高。我们假设利培酮可以抑制可卡因引起的体温过高。科帕卡巴纳注射诱导大鼠体温升高，注射利培酮可显著抑制体温升高。D1和5-HT 2A受体拮抗剂预防可卡因诱导的体温过高;因此，利培酮预防可卡因所致体温升高的能力可能主要归因于其D1和5-HT 2A受体拮抗作用。在微透析研究中，我们发现腹膜内注射可卡因可增加下丘脑前部DA、5-HT和NA水平，利培酮预处理可显著抑制可卡因引起的DA水平的升高。我们的研究结果表明利培酮是一种潜在的治疗可卡因引起的人类急性高热的有效药物。

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.