Kokain bağımlılığında MikroRNA’ların rolü

Bağımlılık genetiği ile ilgili  Nature Nöropsikofarmakoloji Dergisi’nde yayınlanan makale’de, kokain bağımlılığının moleküler, hücresel ve yapısal mekanizmalarında MikroRNA’nın yeri tartışıldı. Makalenin abstraktını ilginize sunuyoruz. -TürkPsikiyatri |

Neuropsychopharmacology Reviews (2013) 38, 198–211; doi:10.1038/npp.2012.120; published online 12 September 2012

Molecular, Cellular, and Structural Mechanisms of Cocaine Addiction: A Key Role for MicroRNAs

Sietse Jonkman1 and Paul J Kenny1

1Laboratory of Behavioral and Molecular Neuroscience, Departments of Molecular Therapeutics and Neuroscience, The Scripps Research Institute–Florida, Jupiter, FL, USA

Correspondence: Dr PJ Kenny, Laboratory of Behavioral and Molecular Neuroscience, Department of Molecular Therapeutics, The Scripps Research Institute—Florida, 130 Scripps Way, Jupiter, FL 33458, USA, Tel: +1 561 228 2231, Fax: +1 561 799 8961, E-mail: pjkenny@scripps.edu

Received 26 March 2012; Revised 4 May 2012; Accepted 8 May 2012
Advance online publication 12 September 2012

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Abstract

The rewarding properties of cocaine play a key role in establishing and maintaining the drug-taking habit. However, as exposure to cocaine increases, drug use can transition from controlled to compulsive. Importantly, very little is known about the neurobiological mechanisms that control this switch in drug use that defines addiction. MicroRNAs (miRNAs) are small non-protein coding RNA transcripts that can regulate the expression of messenger RNAs that code for proteins. Because of their highly pleiotropic nature, each miRNA has the potential to regulate hundreds or even thousands of protein-coding RNA transcripts. This property of miRNAs has generated considerable interest in their potential involvement in complex psychiatric disorders such as addiction, as each miRNA could potentially influence the many different molecular and cellular adaptations that arise in response to drug use that are hypothesized to drive the emergence of addiction. Here, we review recent evidence supporting a key role for miRNAs in the ventral striatum in regulating the rewarding and reinforcing properties of cocaine in animals with limited exposure to the drug. Moreover, we discuss evidence suggesting that miRNAs in the dorsal striatum control the escalation of drug intake in rats with extended cocaine access. These findings highlight the central role for miRNAs in drug-induced neuroplasticity in brain reward systems that drive the emergence of compulsive-like drug use in animals, and suggest that a better understanding of how miRNAs control drug intake will provide new insights into the neurobiology of drug addiction.

Keywords:

cocaine; microRNAs; miR-212; miR-132; BDNF; CREB; MeCP2

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