NAc被公认为是边缘系统和锥体外系运动系统之间的界面部分,与动机行为和奖赏行为密切联系,是成瘾药物的作用基础.阿片类药物,如吗啡,与脑内广泛分布的μ受体结合,直接或间接作用于MLDS中的VTANAc的多巴胺通路,增加NAc多巴胺水平,产生奖赏效应[8].但MLDS尤其是VTANAc多巴胺通路在药物诱发戒断动物复吸中的作用还不清楚.本研究中,NAc毁损组和VTA毁损组中,吗啡注射均未恢复大鼠对吗啡的CPP.说明毁损NAc或VTA能阻断吗啡注射诱发戒断大鼠恢复觅药行为,即复吸.表明NAc和VTA在成瘾药物诱导复吸中起重要作用,提示成瘾药物诱导复吸与MLDS系统中的VTANAc多巴胺通路的激活有关.
Mueller等提出的假说认为,成瘾药物能恢复戒断动物对药物相关刺激的兴趣,导致复吸[9].结合本研究结果,我们认为,长期用药可能引起MLDS系统中的VTANAc多巴胺通路发生敏感化改变,使药物依赖动物表现出行为敏感化.在戒断期,低剂量成瘾药物通过激活MLDS系统中的VTANAc多巴胺通路恢复这些动物对药物相关刺激的兴趣引起药物渴求,导致复吸 .毁损NAc和VTA切断了该通路,阻止了动物恢复对药物相关刺激的兴趣,从而阻断了成瘾药物诱导戒断动物复吸.
复吸是戒毒治疗的难点,高复吸率是毒瘾医学面临的最大挑战.探讨复吸诱发因素及其机制将为制订治疗药物成瘾的方法和策略提供理论依据.研究电毁损神经核团在戒毒中的作用将为外科戒毒提供研究思路.
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