氯胺酮对小鼠吗啡戒断症状和脊髓星形胶质细胞活性的影响

目的 研究氯胺酮对小鼠吗啡戒断症状和脊髓星形胶质细胞活性的影响。方法 昆明种小鼠30只,随机分为5组(n=6),A组:皮下剂量递增法给药建立吗啡依赖模型;B组:对照组,给予等容积的生理盐水;C、D、E3组:吗啡用药均同A组,最后一次吗啡注射30 min后分别腹腔注射0、8、16 mg/kg氯胺酮。观察纳络酮催瘾后戒断症状的改变;用免疫组化方法测定各组脊髓星形胶质细胞胶质纤维酸性蛋白(GFAP)免疫反应阳性产物的变化。结果 与C组相比,D组可缓解吗啡戒断症状(P<0.05),而E组则明显缓解(P<0.01);D组和E组吗啡戒断所致的体重下降显著减轻(P<0.01)。脊髓GFAP免疫反应阳性产物表达相对面积,A组与B组比较,D、E组与C组比较差异均无显著性意义(均为P>0.05)。结论 氯胺酮可缓解小鼠吗啡戒断症状,脊髓星形胶质细胞GFAP活性可能未参与介导吗啡依赖和戒断反应。

Effects of Ketamine on Naloxone-precipitated Morphine Withdrawal Responses and Spinal Astrocyte Activity in Mice

Objective To investigate the effects of ketamine on naloxone- precipitated morphine withdrawal symptoms and spinal astrocyte activity in mice. Methods Thirty Kunming mice were randomly divided into 5 groups of 6 animals each: Group A, morphine dose-dependent model by subcutaneous injection of morphine hydrochloride: group B, receiving the same volume of saline intraperitoneally; Groups C, D, E receiving the same dose of morphine as group group A but with addition of ketamine at concentration of 0, 8 and 16 mg/kg 30 min respectively after finally intraperitoneal injection of morphine. Naloxone-precipi-tated morphine withdrawal symptoms were observed in morphine-dependent mice. The changes of the spinal astrocytes were detected by immunohistochemistry SABC method. Results In groups D and E, ketamine could significantly attenuate the withdrawal behaviors. Weight loss was attenuated by ketamine in groups D and E. No significant difference in the GFAP immunoreactive cells was found between group A and group B, between group C and group E. Conclusion Ketamine could significantly attenuate naloxone-precipitated morphine withdrawal responses, and there were no close relations between withdrawal responses and spinal astrocyte activity.