伏隔核的外壳部和核心部毁损对大鼠吗啡觅药行为的影响

摘要

背景:伏隔核对吗啡觅药行为的建立起着至关重要的作用,而伏隔核内不同区域在形态学、神经化学和电生理学等方面存在明显差别.目的:分析伏隔核各亚区(外壳、核心)在吗啡觅药行为中的作用,研究定向毁损对大鼠成瘾行为的影响.设计:随机对照实验研究.地点和对象:雄性Sprague-Dawley大鼠,由解放军第四军医大学实验动物中心提供.干预:大鼠通过吗啡强化形成条件性地点偏好,在反应稳定后,使用直流电对大鼠进行外壳部或核心部毁损(或空白对照).待大鼠恢复后进行吗啡复燃,并测试其地点偏好数据.主要观察指标:位置偏爱箱内最大停留时间.结果:在7 d内,所有外壳毁损组和空白对照组动物均重新建立起了与毁损前相同的条件性地点偏好,最大停留时间分别为(647±46)和(662±29)s,均达到术前水平.但是,伏隔核核心部毁损却导致觅药行为的明显减退,最大停留时间由术前的(650±30)s减至术后的(463±40)s,与其他两组相比差异有显著性意义(q=3.95,4.17;P＜0.05).结论:在药物相关刺激条件下,伏隔核核心在吗啡觅药行为的建立方面起重要作用.%BACKGROUND:Nucleus accumbens septi plays a very important role in the acquisition of drug-seeking behavior under morphine reinforcement, but different regions in the nucleus accumbens septi have great differences in morphology, neurochemistry and electrophysiology.OBJECTIVE: To investigate the function of the sub-regions of the nucleus accumbens septi(core or shell) in drug-seeking behavior and the effects of oriented lesion on drug addiction.DESIGN: A randomized controlled experimental research.SETTING and MATERIALS: The Experimental Animal Center of Fourth Military Medical University of Chinese PLA provided male SpragueDawley rats.INTERVENTIONS: Rats were trained to acquire conditioned place preference(CPP) under morphine reinforcement. After response was established, rats were given direct current to cause lesions in either the core or shell of the nucleus accumbens septi(or blank control). And when recovery was gained, rats were assessed for their regain of CPP under morphine reinforcement.MAIN OUTCOME MEASURES: The longest staying time in place preference box.RESULTS: Within 7 days, the shell lesion group and the sham group re-acquired CPP that was the same as that before lesion. The longest staying time was(647 ±46) and(662±29) s respectively, and both achieved pre-operation levels. However, rats with lesions in the core of the nucleus accumbens septi were severely impaired in the acquisition of morphine-seeking behavior. The longest staying time was reduced from (650 ± 30) s before operation to(463 ± 40) s after operation. A significant difference was found, compared with the other two groups( q = 3.95,4.17;P<0.05).CONCLUSION: These results indicate animportant role of the core of the nucleus accumbens septi in the acquisition of drug-seeking behavior under the control of drug-associated stimuli.