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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)(P<0.01);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(P<0.05),而核部的p-CREB表达显著增加(P<0.01)。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。
Objective To observe the effects of Clenbuterol, a β2 adrenergic receptor agonist, injected into the subrethral cortex (IL) on the relapse behavior of heroin in rats. Methods Adult male Sprague-Dawley rats were trained on self-administration of heroin by a fixed ratio F1 program for 4 days a day for 14 consecutive days to establish their own model of heroin administration. Subsequent daily 2 h of the environment subsided until it reached the fade criteria. Microinjection of clenbuterol into each brain region of IL was performed for 8 min. After 15 minutes, clue-induced drug-seeking behavior of heroin was determined and autonomic motor activity was observed. The brain tissue was sacrificed immediately after the behavioral test. Western blotting was used to detect the expression of phosphorylated cAMP response element binding protein (p CREB) in the marginal cortex, IL, nucleus accumbens and nucleus. Results In the randomized heroin seeking behavior test, the effective nasal contact number (8 ± 3) in the Clenbuterol group was significantly lower than that in the model group (45 ± 10) (P <0.01). In the 2 h spontaneous activity test , While there was no significant difference in spontaneity of Clenbuterol group (1557 ± 369) compared with model group (1514 ± 264). Western blotting showed that compared with model group, clenbuterol group The expression of p-CREB was significantly decreased in both IL and nucleocapsid (P <0.05), while the expression of p-CREB in nucleus was significantly increased (P <0.01). Conclusion Microinjection of clenbuterol into IL can significantly inhibit the resuscitation of heroin-treated rats, and its inhibitory effect may be related to the alteration of p CREB expression in the nucleus and nucleus of the nucleus accumbens.