长期使用可卡因诱发脑中发生若干结构和功能变化，它们有可能导致强迫性吸毒，但调控这一过程的机制尚不清楚。现在，用大鼠所做实验揭示了纹状体中的微RNA在主管强迫性可卡因吸食行为的形成中所起的一个根本性作用。
microRNA "miR-212"能够降低对可卡因的欲望，但只是在长期使用该药物的大鼠身上才会是这样，而不是在对该药物没有依赖性的大鼠身上。miR-212似乎是通过放大转录因子CREB（可卡因奖励效应的一个已知的调控因子）的活性来发挥作用的。这项工作提出一个可能性：调控非编码RNA的药物也许能够有效逆转药物上瘾。(生物谷Bioon.net)
生物谷推荐原文出处：
Nature doi:10.1038/nature09202
Striatal microRNA controls cocaine intake through CREB signalling
Jonathan A. Hollander,Heh-In Im,Antonio L. Amelio,Jannet Kocerha,Purva Bali,Qun Lu,David Willoughby,Claes Wahlestedt,Michael D. Conkright& Paul J. Kenny
Cocaine addiction is characterized by a gradual loss of control over drug use, but the molecular mechanisms regulating vulnerability to this process remain unclear. Here we report that microRNA-212 (miR-212) is upregulated in the dorsal striatum of rats with a history of extended access to cocaine. Striatal miR-212 decreases responsiveness to the motivational properties of cocaine by markedly amplifying the stimulatory effects of the drug on cAMP response element binding protein (CREB) signalling. This action occurs through miR-212-enhanced Raf1 activity, resulting in adenylyl cyclase sensitization and increased expression of the essential CREB co-activator TORC (transducer of regulated CREB; also known as CRTC). Our findings indicate that striatal miR-212 signalling has a key role in determining vulnerability to cocaine addiction, reveal new molecular regulators that control the complex actions of cocaine in brain reward circuitries and provide an entirely new direction for the development of anti-addiction therapeutics based on the modulation of noncoding RNAs.
