药物成瘾神经生物学机制研究获新进展

2013-02-06 梁建辉等 《脑研究》

  作为研究药物成瘾神经生物学机制的一种动物模型,行为敏化已日益受到人们的关注。近日,北京大学中国药物依赖性研究所教授梁建辉带领课题组,通过实验发现了单针吗啡诱导小鼠行为敏化的新的神经生物学机制。相关成果发表在《国际神经精神药理学》、《脑研究》(Brain Research)等国际学术期刊上。   “这个结果让我们既高兴又沮丧。”梁建辉在接受《中国科学报》记者采访时表示,高兴在于对于吗啡等精神活

  作为研究药物成瘾神经生物学机制的一种动物模型,行为敏化已日益受到人们的关注。近日,北京大学中国药物依赖性研究所教授梁建辉带领课题组,通过实验发现了单针吗啡诱导小鼠行为敏化的新的神经生物学机制。相关成果发表在《国际神经精神药理学》、《脑研究》(Brain Research)等国际学术期刊上。

  “这个结果让我们既高兴又沮丧。”梁建辉在接受《中国科学报》记者采访时表示,高兴在于对于吗啡等精神活性物质成瘾研究有了最新发现;沮丧则因为实验结果从新的角度证明:戒毒太难了!

  梁建辉介绍了整个实验的过程:20只小鼠被分成两组,一组注射20毫克吗啡,另一组注射生理盐水。经过7~21天,吗啡组小鼠体内吗啡早已代谢干净,此时给两组小鼠同时注射5毫克吗啡,前期给予吗啡的小鼠行为应答显著强于生理盐水组,表明出现行为敏化效应。

  据悉,与吗啡相似,单次暴露于可卡因、甲基苯丙胺等精神活性物质的大鼠也表现出长期自主活动增强。

  “这意味着,仅仅一针吗啡,就改变了动物对药物的反应和外在行为,而且是长期改变。”梁建辉说。

  以往戒毒针可以对药物成瘾和心理依赖两个方面进行介入治疗和疏导,但毒品对于长期行为的影响,目前还没有科学的方法能够提供介入帮助或治疗。这让人们对戒毒之难有了更深层次的认识。

  在此模型基础上,课题组进一步探讨单针吗啡诱导小鼠行为敏化的神经生物学机制,研究结果表明单针吗啡诱导小鼠行为敏化的形成涉及脑内的部分关键性核团、新的基因转录、新的蛋白合成以及组蛋白乙酰化修饰的改变。

  结合行为学和分子生物学实验的结果,课题组发现了1个与单针吗啡诱导的小鼠行为敏化效应密切相关的脑核团——隔核及相关基因Hsp70和COX2。

  Hsp70是一种应激诱导蛋白,作为分子伴侣与蛋白质结合从而调节蛋白质的构型、跨膜转运、配体受体结合或酶活性;而关于COX2在吗啡依赖中的作用,其具体机制还有待进一步研究。



    

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