長(zhǎng)期使用可卡因誘發(fā)腦中發(fā)生若干結(jié)構(gòu)和功能變化,，它們有可能導(dǎo)致強(qiáng)迫性吸毒,，但調(diào)控這一過(guò)程的機(jī)制尚不清楚。現(xiàn)在,，用大鼠所做實(shí)驗(yàn)揭示了紋狀體中的微RNA在主管強(qiáng)迫性可卡因吸食行為的形成中所起的一個(gè)根本性作用,。
microRNA "miR-212"能夠降低對(duì)可卡因的欲望,，但只是在長(zhǎng)期使用該藥物的大鼠身上才會(huì)是這樣，而不是在對(duì)該藥物沒(méi)有依賴性的大鼠身上,。miR-212似乎是通過(guò)放大轉(zhuǎn)錄因子CREB（可卡因獎(jiǎng)勵(lì)效應(yīng)的一個(gè)已知的調(diào)控因子）的活性來(lái)發(fā)揮作用的,。這項(xiàng)工作提出一個(gè)可能性：調(diào)控非編碼RNA的藥物也許能夠有效逆轉(zhuǎn)藥物上癮。(生物谷Bioon.net)
生物谷推薦原文出處：
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.
