CCK-8及其受体拮抗剂对吗啡戒断大鼠额叶皮质、尾壳核、海马μ阿片受体的影响

Effects of CCK-8 and its receptor antagonists on μ-opioid receptor in prefrontal cortex,cauduate putamen and hippocampus of morphine withdrawal rats

目的通过观察CCK-8及其受体拮抗剂对吗啡戒断大鼠额叶皮质、尾壳核、海马μ阿片受体的影响,初步探讨CCK-8对吗啡戒断症状的影响及其受体机制。方法建立大鼠吗啡慢性依赖及纳络酮催促戒断模型,观察CCK-8及CCK1受体拮抗剂L-364,718、CCK2受体拮抗剂LY-288,513慢性干预对戒断症状的影响,并采用放射配基结合法测定额叶皮质、尾壳核、海马μ阿片受体的结合活性,即受体数量(Bmax)及结合力(Kd)。结果①给予吗啡前腹腔注射CCK-8及CCK受体拮抗剂慢性干预均可减轻吗啡戒断症状;②慢性吗啡作用后,额叶皮质和海马μ阿片受体数量及结合力下降,而尾壳核μ阿片受体数量无变化,仅结合力降低;戒断后,额叶皮质、尾壳核μ阿片受体数量及结合力升高,而海马μ阿片受体数量无变化,仅结合力升高;③CCK-8及其受体拮抗剂慢性干预后,使吗啡戒断大鼠尾壳核μ阿片受体结合力降低、海马μ阿片受体数量增加,但是对额叶皮质μ阿片受体的结合活性无影响。结论 CCK-8及其受体拮抗剂可通过调节μ阿片受体减轻吗啡戒断症状,并具有脑区特异性。

Aim To explore the receptor mechanisms that CCK-8 regulates morphine withdrawal syndrome,and to observe the effects of CCK-8 and CCK receptor antagonists on μ-opioid receptor in PFC,CPu and Hip of morphine withdrawal rats.Methods After establishing rat models for morphine dependence and naloxone-precipitated withdrawal,the effects of CCK-8,L-364,718,CCK1 receptor antagonist,LY-288,513,CCK2 receptor antagonist pretreatments on the morphine withdrawal syndrome were observed,and the binding capacity Bmax and apparent affinity Kd of μ-opioid receptor in cortex,caudate putamen and hippocampus were tested by Radioligand binding assay.Results ① Intraperitoneal injections of CCK-8 and CCK receptor antagonists before morphine treatments were able to reduce the withdrawal severity.② Chronic morphine treatment attenuated the capacity and affinity of μ-opioid receptor in PFC and Hip,but it had no effect on the capacity of μ-opioid receptor in CPu,only attenuating the affinity.After naloxone treatment,the capacity and affinity were both upregulated in PFC and CPu.But in Hip,the capacity of μ-opioid receptor was not changed,only the affinity increased.③ CCK-8 and its antagonists could effectively attenuate the affinity of μ-opioid receptor in CPu and escalate the capacity in Hip of morphine withdrawal rats,while they could not regulate μ-opioid receptor in PFC.Conclusion Both CCK-8 and CCK receptor antagonists can alleviate morphine withdrawal symptoms by regulating μ-opioid receptor,with specificity in different brain regions.