八肽胆囊收缩素及其受体拮抗剂对吗啡戒断大鼠脑内[Ca^(2+)]_i和CaM活性的影响

Effecs of CCK-8 and its receptor antagonists on [Ca^(2+)]_i and CaM activity in morphine withdrawal rats

目的观察八肽胆囊收缩素(CCK-8)及其受体拮抗剂对吗啡戒断大鼠皮质、海马、纹状体神经细胞内[Ca2+]i和CaM活性的影响。方法剂量递增法(10~50 mg·kg-1)连续5 d皮下注射吗啡建立吗啡依赖模型,并给予腹腔注射纳洛酮(5 mg·kg-1)催促戒断,采用流式细胞术检测大鼠皮质、海马、纹状体[Ca2+]i和CaM活性的变化。结果 (1)与盐水对照组相比,吗啡依赖组大鼠皮质、海马、纹状体内[Ca2+]i和CaM活性均明显升高;纳洛酮催促戒断后[Ca2+]i和CaM活性较吗啡依赖组均明显降低;(2)CCK-8及CCK-1受体拮抗剂L-364,718、CCK-2受体拮抗剂LY-288,513均使吗啡戒断大鼠海马和纹状体内[Ca2+]i和CaM活性明显升高,但皮质内[Ca2+]i和CaM活性无明显变化。结论 CCK-8及其受体拮抗剂对吗啡依赖大鼠戒断反应的作用可能与其对相关脑区神经细胞内[Ca2+]i和CaM活性的调节有关。

Aim To observe the effect of CCK-8 and its receptor antagonists on [ Ca^2＋ ] i and CaM activity in prefrontal cortex （ PFC ） , hippocampus （ Hip ） and cauduate putamen（CPu） of morphine withdrawal rats. Methods A physical morphine-dependent model in rats was established by subcutaneous injection of mor- phine in gradually increasing doses for 5 consecutive days. The [ Ca2＋ ]i and CaM activity in cortex, hippo- campus and striatum of rats were assayed by flow cy- tometry. Results （1） .Compared with control group, morphine dependence significantly increased [ Ca2＋ ] i and CaM activity in cortex, hippocampus and striatum. Following naloxone precipitation, the [ Ca^2＋ ] i and CaM activity significantly decreased. （2） CCK-8 and its receptor antagonists treatment significantly increased [ Ca2 ＋ ] i and CaM activity in hippocampus and striatum of morphine withdrawal rats, but they had no effect on Ca2 ＋ ] i and CaM activity in cortex. Conclusion The inhibitory effect of CCK-8 and its receptor antagonists on withdrawal syndrome of morphine-dependent rats may be related to the increase of Ca^2＋ i and CaM ac- tivity in specific brain regions.