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 and Paul J. Kenny ()
Additional contact information
Jonathan A. Hollander: Laboratory of Behavioral and Molecular Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458, USA
Heh-In Im: Laboratory of Behavioral and Molecular Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458, USA
Antonio L. Amelio: The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458, USA
Jannet Kocerha: The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458, USA
Purva Bali: Laboratory of Behavioral and Molecular Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458, USA
Qun Lu: Laboratory of Behavioral and Molecular Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458, USA
David Willoughby: Ocean Ridge Biosciences, 10475 Riverside Drive, Palm Beach Gardens, Florida 33410, USA
Claes Wahlestedt: The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458, USA
Michael D. Conkright: The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458, USA
Paul J. Kenny: Laboratory of Behavioral and Molecular Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458, USA

Nature, 2010, vol. 466, issue 7303, 197-202

Abstract: Abstract 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.

Date: 2010
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature09202 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:466:y:2010:i:7303:d:10.1038_nature09202

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature09202

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().