.Molecular Psychiatry :复旦大学发现吗啡奖赏作用神经机制

2019-08-19 黄辛 科学网

复旦大学脑科学研究院马兰教授团队一项最新研究发现吗啡能协同激活大脑皮层中两类不同的中间神经元,造成抑制性神经环路的持续失活,从而揭示了吗啡等成瘾性药物产生强烈奖赏和依赖作用的神经机制。8月14日,这一研究成果在线发表于《自然》杂志子刊《分子精神病学》(Molecular Psychiatry)。


复旦大学脑科学研究院马兰教授团队一项最新研究发现吗啡能协同激活大脑皮层中两类不同的中间神经元,造成抑制性神经环路的持续失活,从而揭示了吗啡等成瘾性药物产生强烈奖赏和依赖作用的神经机制。8月14日,这一研究成果在线发表于《自然》杂志子刊《分子精神病学》(Molecular Psychiatry)。

吗啡等阿片类药物具有良好的镇痛作用,但其同时能产生强烈的奖赏作用(欣快感),因此会导致成瘾甚至滥用。研究表明,吗啡等阿片类药物通过激活细胞表面的阿片受体而发挥作用。脑内大部分神经元是兴奋性神经元。以往的研究表明,阿片类药物给药后,引起兴奋性神经元形态和功能可塑性的长期改变,这被认为是其药理作用和成瘾的基础。然而大脑皮层中还存在中间神经元,虽然在数量上只占神经元的一小部分,但所介导的抑制性突触传递,在调控兴奋性突触传递和环路整合中发挥关键作用,其功能异常将导致精神疾病。

马兰团队研究发现,吗啡能激活PV中间神经元上的m-阿片受体,直接减弱对兴奋性神经元的抑制,吗啡还同时通过激活SST中间神经元上的d-阿片受体,增强其对PV神经元的抑制,进一步削弱PV对兴奋性神经元的抑制。这一研究首次揭示了吗啡通过作用于两种中间神经元上不同的阿片受体,协同调控抑制性微环路,以直接和间接的方式,削弱前边缘大脑皮层对兴奋性神经元的抑制性输入,使其持续去抑制,从而产生异常强烈奖赏作用的机制,并为研发低成瘾性阿片类镇痛药物提供了新的思路。

该研究得到科技部973计划“精神活性物质成瘾记忆的形成和消除”项目、国家自然科学基金重点项目和重大研究计划集成项目资助。复旦大学脑科学研究院2019届博士生江长优为论文第一作者,复旦大学脑科学研究院马兰教授和基础医学院王菲菲教授为论文共同通讯作者。

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    2019-08-21 showtest
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    2019-08-21 saikp

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