新一期英国《自然》(Nature)杂志一篇研究报告说，动物实验显示，可卡因成瘾与脑部特定区域神经元活动偏弱有关，刺激这一区域有助于减少对可卡因的依赖。这一成果为开发戒毒新方法提供了思路。
美国国家吸毒研究所研究人员报告说，他们对可卡因成瘾的实验鼠大脑进行研究后发现，这些实验鼠大脑前额叶皮质的某一区域神经元活动明显偏弱。此前研究发现，人脑中的相应区域与行为控制能力有关，该区域受损或有缺陷者更容易对可卡因上瘾，戒除毒瘾也更困难。
实验中，研究人员用光遗传学技术对实验鼠中“瘾君子”脑部的这一区域进行刺激，发现这些实验鼠寻求可卡因的行为有所减少。相反，如果抑制该区域神经元的活动，实验鼠则表现出毒瘾增强的迹象。光遗传学技术是将光与遗传工程相结合，可改变神经细胞的活性。
研究人员说，这一结果表明，大脑前额叶皮质特定区域的神经元活性与可卡因成瘾有密切关系，通过刺激该区域的神经元可有效提高对毒瘾的控制能力，这将有助于开发新疗法，帮助人们戒除毒瘾。(生物谷Bioon.com)
doi:10.1038/nature12024
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Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking
Billy T-Chen, Hau-Jie Yau, Christina Hatch,Ikue Kusumoto-Yoshida,Saemi L-Cho, F-Woodward Hopf, Antonello Bonci.
Loss of control over harmful drug seeking is one of the most intractable aspects of addiction, as human substance abusers continue to pursue drugs despite incurring significant negative consequences1. Human studies have suggested that deficits in prefrontal cortical function and consequential loss of inhibitory control2, 3, 4 could be crucial in promoting compulsive drug use. However, it remains unknown whether chronic drug use compromises cortical activity and, equally important, whether this deficit promotes compulsive cocaine seeking. Here we use a rat model of compulsive drug seeking5, 6, 7, 8 in which cocaine seeking persists in a subgroup of rats despite delivery of noxious foot shocks. We show that prolonged cocaine self-administration decreases ex vivo intrinsic excitability of deep-layer pyramidal neurons in the prelimbic cortex, which was significantly more pronounced in compulsive drug-seeking animals. Furthermore, compensating for hypoactive prelimbic cortex neurons with in vivo optogenetic prelimbic cortex stimulation significantly prevented compulsive cocaine seeking, whereas optogenetic prelimbic cortex inhibition significantly increased compulsive cocaine seeking. Our results show a marked reduction in prelimbic cortex excitability in compulsive cocaine-seeking rats, and that in vivo optogenetic prelimbic cortex stimulation decreased compulsive drug-seeking behaviours. Thus, targeted stimulation of the prefrontal cortex could serve as a promising therapy for treating compulsive drug use.
