Nature子刊：沉默突触，瘾君子的新希望

　　

生物通报道：想想看如果只要吃片药就能彻底戒掉可卡因，那该有多好啊。Pittsburgh大学的一项新研究向人们展示，通过药物对特定神经回路进行操作，有望削弱瘾君子们对可卡因的依赖。文章发表在Nature旗下的Nature Neuroscience杂志上。

Pittsburgh大学的神经学助理教授Yan Dong领导研究团队在大鼠模型中进行实验。伏隔核（nucleus accumbens）是大脑中与奖赏、情感、激励和成瘾有关的小区域通。研究人员分析了可卡因成瘾和戒除可卡因，对上述区域神经细胞的影响。他们主要针对突触的作用进行研究，突触是神经细胞末端负责传递信号的结构。

当个体服用可卡因时，会产生一些不成熟的突触。由于这些突触在正常生理条件下基本不发送信号，因此它们也被称为“沉默突触”。一旦个体停止使用可卡因，上述沉默突触就会进入成熟期，获得了发送信号的能力。当个体再度面临吸毒的诱惑时，这些突触就会发送信号，引起个体对可卡因的强烈渴望。

研究人员指出，如果能够逆转这些突触的成熟，就能让它们继续保持沉默，帮助个体彻底戒除对可卡因的依赖。研究显示，沉默突触的成熟需要一个重要的化学受体，CP-AMPAR。于是，研究人员去除了CP-AMPAR受体，这一措施成功使突触回到了沉默状态。

“逆转沉默突触的成熟过程，可以抑制个体对可卡因的强烈渴望，”文章通讯作者Dong说。“我们正在开发生物学和药理学策略，希望能够长期维持沉默突触的去成熟效果。”

 

（生物通编辑：叶予）

生物通推荐原文摘要：

Maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving

In rat models of drug relapse and craving, cue-induced cocaine seeking progressively increases after withdrawal from the drug. This 'incubation of cocaine craving' is partially mediated by time-dependent adaptations at glutamatergic synapses in nucleus accumbens (NAc). However, the circuit-level adaptations mediating this plasticity remain elusive. We studied silent synapses, often regarded as immature synapses that express stable NMDA receptors with AMPA receptors being either absent or labile, in the projection from the basolateral amygdala to the NAc in incubation of cocaine craving. Silent synapses were detected in this projection during early withdrawal from cocaine. As the withdrawal period progressed, these silent synapses became unsilenced, a process that involved synaptic insertion of calcium-permeable AMPA receptors (CP-AMPARs). In vivo optogenetic stimulation–induced downregulation of CP-AMPARs at amygdala-to-NAc synapses, which re-silenced some of the previously silent synapses after prolonged withdrawal, decreased incubation of cocaine craving. Our findings indicate that silent synapse–based reorganization of the amygdala-to-NAc projection is critical for persistent cocaine craving and relapse after withdrawal.