糖皮质激素受体对大鼠丙泊酚依赖行为的影响及其机制  

The effect of glucocorticoid receptor on propofol self-administration of rats and its mechanisms

作　　者：董张雷 梁宇渊 苏颖 林函[1] 王本福[1] DONG Zhanglei;LIANG Yuyuan;SU Ying;LIN Han;WANG Benfu(Department of Anesthesiology,the Second Afflliated Hospital&Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou 325027,China)

机构地区：[1]温州医科大学附属第二医院育英儿童医院麻醉与围术期医学科,浙江温州325027

出　　处：《温州医科大学学报》2020年第12期966-969,共4页Journal of Wenzhou Medical University

基　　金：国家自然科学基金资助项目(81771431);温州市科技局科研基金资助项目(Y20160365)。

摘　　要：目的:研究糖皮质激素受体(GR)对大鼠丙泊酚觅药行为的影响,探讨丙泊酚精神依赖性的发生机制。方法:24只SD大鼠用固定比率(FR1)强化程序建立丙泊酚精神依赖性模型,并随机均分为对照组、RU48610 mg/kg组、RU48620 mg/kg组和RU48640 mg/kg组,观察腹腔注射不同剂量GR拮抗剂RU486对大鼠自身觅药行为学的影响,Western blot检测大鼠伏隔核(NAc)内多巴胺转运体(DAT)的蛋白表达水平。另取24只SD大鼠用FR1程序建立自身给予蔗糖行为模型后随机均分为对照组、RU48610 mg/kg组、RU48620 mg/kg组和RU48640 mg/kg组,观察腹腔注射不同剂量GR拮抗剂RU486对大鼠自身给予蔗糖行为的影响。结果:与对照组比,GR拮抗剂RU486腹腔给药可剂量依赖性减弱大鼠丙泊酚自身觅药行为(P<0.01),并降低大鼠NAc内DAT的蛋白水平表达(P<0.05)。与对照组比,RU486腹腔给药不影响大鼠自身给予蔗糖行为(P>0.05)。结论:GR拮抗剂可能通过影响NAc内DAT水平从而减弱大鼠丙泊酚觅药行为。Objective:To determine whether glucocorticoid receptor involves in propofol self-administration of rats,so as to offer reference for clinical prevention and treatment.Methods:In one experimental group,twenty-four Sprague-Dawley rats were trained to self-administer propofol under a fixed ration(FR1)schedule of reinforcement for 14 d.Then,the rats were treated with saline(control group)and RU486,a GR antagonist(10,20,40 mg/kg)at 1 h prior to the last training to observe the change of animal behavior.Western blot was used to detect the dopamine DAT level in NAc of propofol dependent.In the other experimental group,twenty-four rats were trained to nose-poke for sucrose pellets under FR1 schedule of reinforcement of a daily 0.5-h session for successive 7 days.Thenthe trained rats received intraperitoneally either saline or a dose of RU486(10,20,40 mg/kg)at 1 h prior to the last training to observe the change of animal behavior.Results:RU486 significantly decreased the number of injections and active responses(P<0.01),which was associated with the large decrease in DAT of NAc(P<0.05).However,the food-maintaining sucrose responses under FR1 schedule was not affected by any doses of RU486 tested(P>0.05).Conclusion:The present results indicate that RU486 may counteract the reinforcing properties of propofol,playing an important role in the incubation of propofol dependent by influencing the dopamine DAT levels.

关 键 词：RU486 丙泊酚 自身给药 多巴胺转运体 大鼠 

分 类 号：R749.6[医药卫生—神经病学与精神病学]