边缘下皮质脑区微注射克仑特罗对线索诱导海洛因复吸的抑制作用

发布时间：2018-11-03 19:30

【摘要】：目的观察边缘下皮质(IL)脑区注射β2肾上腺素受体激动剂克仑特罗对海洛因自身给药大鼠复吸行为的影响。方法成年雄性SD大鼠采用固定比率F1程序进行海洛因自身给药训练,每天4 h,连续14 d,建立海洛因自身给药模型。随后每天进行2 h环境消退,直至达到消退标准。每侧IL脑区微注射克仑特罗8 ng,15 min后进行线索诱导的海洛因觅药行为的测定,观察大鼠自主运动情况。行为测试结束后立即处死取脑组织,Western蛋白印迹法检测边缘前皮质、IL、伏隔核壳部及核部脑区磷酸化c AMP反应元件结合蛋白(p CREB)表达水平变化。结果在线索诱导的海洛因觅药行为测试中,克仑特罗组的有效鼻触数(8±3)显著低于模型组(45±10)(P0.01);2 h自发活动度检测中,克仑特罗组大鼠自发活动度(1557±369)和模型组(1514±264)相比无显著性差异;Western蛋白印迹法检测显示,与模型组相比,克仑特罗组大鼠的IL和伏隔核壳部的p-CREB表达均明显减少(P0.05),而核部的p-CREB表达显著增加(P0.01)。结论IL脑区微注射克仑特罗可显著抑制海洛因自身给药大鼠的复吸行为,其抑制作用可能与伏隔核壳部和核部p CREB表达改变有关。
[Abstract]:Objective to observe the effect of clenbuterol, a 尾 2 adrenoceptor agonist, injected into (IL) area of inferior marginal cortex on relapse behavior of heroin self-administered rats. Methods the adult male SD rats were given heroin self-administration training with a fixed ratio F1 program for 4 hours a day for 14 consecutive days to establish a heroin self-administration model. Then the environment subsided for 2 hours every day until the standard of extinction was reached. After microinjection of clenbuterol for 8 ng,15 min on each side of IL, the drug seeking behavior induced by clues was measured and the spontaneous movement of rats was observed. Brain tissue was killed immediately after behavioral test. The expression of phosphorylated c AMP response element binding protein (p CREB) in the prelimbic cortex, the putamen of the nucleus accumbens and the nucleus of IL, was detected by Western blot. Results the effective nasal contacts in clenbuterol group (8 卤3) were significantly lower than those in model group (45 卤10) (P0.01). There was no significant difference in spontaneous activity between clenbuterol group (1557 卤369) and model group (1514 卤264). Compared with the model group, the expression of IL and p-CREB in nucleus accumbens of clenbuterol group was significantly decreased (P0.05), while the expression of p-CREB in nucleus was significantly increased (P0.01). Conclusion Clenbuterol in IL brain area can significantly inhibit the relapse behavior of heroin self-administered rats, and its inhibitory effect may be related to the changes of p CREB expression in nucleus putamen and nucleus of nucleus accumbens.
【作者单位】：宁波市鄞州区同济中学;宁波市微循环与莨菪类药研究所宁波戒毒研究中心;宁波大学医学院;
【基金】：国家自然科学基金重点项目(U1132602) 浙江省自然科学基金面上项目(LY14H310002) 宁波市科技计划项目(2013C50033)~~
【分类号】：R965

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