氯胺酮对大鼠吗啡戒断症状的影响及其作用机理

目的　研究氯胺酮对大鼠吗啡戒断症状的影响及其可能的机理。方法　建立大鼠吗啡依赖模型 ,在用纳洛酮催瘾前 2min给予不同剂量的氯胺酮 ,观察其戒断症状的改变 ;用分光光度法测定戒断时大鼠一氧化氮 (NO)含量、一氧化氮合酶 (NOS)活性 ,用放射免疫法测定环鸟苷酸 (cGMP)含量。结果　 3个剂量的氯胺酮 (5、10和 2 0mg·kg- 1)均可缓解吗啡戒断时探究、扭体、湿狗样抖动、跳跃等运动反应 ,减少活动次数 ,抑制植物神经系统症状。10、2 0mg·kg- 1氯胺酮可显著减轻吗啡戒断所致的体重下降 ,小剂量氯胺酮 (5mg·kg- 1)可抑制吗啡依赖大鼠前额叶皮质、小脑的NOS活性和NO、cGMP含量的增高。结论　氯胺酮可缓解大鼠吗啡戒断症状 ,其作用机理可能与减弱大鼠吗啡戒断时NMDA NO cGMP通路效应有关。

Effects of ketamine on precipitated morphine withdrawal symptoms in rats and its possible mechanism

AIM To elucidate the effects of ketamine on naloxone- precipitated morphine withdrawal symptoms in rats and its possible mechanism. METHODS Naloxone-precipitated morphine withdrawal symptoms were observed in morphine- dependent rats. Various doses of ketamine or normal saline were administrated ip to rats 2 min before the test. Nitric oxide synthase(NOS) activity and nitric oxide(NO) output were assessed with spectrophotometric analysis, concentration of cyclic guanosine monophosphate(cGMP) was measured with radioimmunoassay. RESULTS Ketamine(5, 10, 20 mg·kg^-1, ip)can significantly attenuate the counted withdrawal behaviors(numbers of jumps, wet dog shakes, rearing as well as writhing movements); various doses of ketamine effectively inhibited autonomic hyperactivity such as salivation, tearing, diarrhea(P＜0.05); weight loss across the abstinence session was attenuated by ketamine at the doses of 10, 20 mg·kg^-1(P＜0.05). Levels of NOS activity, NO output as well as cGMP content in cerebellum, prefrontal cortex during the period of morphine withdrawal were increased significantly compared with saline group (P＜0.05), while pretreatment of ketamine could inhibit the enhanced NOS activity, NO output as well as concentration of cGMP in morphine abstinence session(P＜0.05). CONCLUSION Withdrawal symptoms in morphine dependent rats can be attenuated by pretreatment of ketamine, the mechanism may be related to the suppression of up-regulation of NMDA-NO-cGMP signaling pathway.