Striatal microRNA controls cocaine intake through CREB signalling.
Striatal microRNA controls cocaine intake through CREB signalling.
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作者：
可卡因成瘾的特点是逐渐失去对药物使用的控制，但调节这一过程脆弱性的分子机制尚不清楚。在这里，我们报告了microRNA-212 （miR-212）在长期接触可卡因的大鼠背纹状体中上调。纹状体miR-212通过显著放大药物对CREB信号的刺激作用，降低了对可卡因动机特性的反应性。这种作用是通过mir -212增强Raf-1活性发生的，导致腺苷酸环化酶增敏和必需的CREB共激活物TORC（受调节CREB的传感器，也称为CRTC）的表达增加。我们的研究结果表明纹状体miR-212信号在决定可卡因成瘾易感性中起着关键作用，揭示了控制可卡因在大脑奖赏回路中复杂作用的新分子调节因子，并为基于非编码rna调节的抗成瘾治疗的发展提供了全新的方向。
Cocaine addiction is characterized by a gradual loss of control over drug use, but 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 dramatically amplifying the stimulatory effects of the drug on CREB signaling. This action occurs through miR-212-enhanced Raf-1 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 suggest that striatal miR-212 signaling plays a key role in determining vulnerability to cocaine addiction, reveal novel 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 modulation of noncoding RNAs.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
82.9
作者：
Altarejos, Judith Y.;Goebel, Naomi;Conkright, Michael D.;Inotiel, Hiroshi;Xie, Jianxin;Arias, Carlos M.;Sawchenko, Paul E.;Montminy, Marc
通讯作者：
Montminy, Marc
影响因子：
2.3
作者：
Anthony, James C.;Warner, Lynn A.;Kessler, Ronald C.
通讯作者：
Kessler, Ronald C.
影响因子：
64.8
作者：
King, AJ;Sun, HY;Marshall, MS
通讯作者：
Marshall, MS
DOI：
10.1073/pnas.0805854106
发表时间：
2009-03-03
影响因子：
11.1
作者：
Kocerha, Jannet;Faghihi, Mohammad Ali;Wahlestedt, Claes
通讯作者：
Wahlestedt, Claes