MicroRNAs and drug addiction

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53 Scopus citations

Abstract

Drug addiction is considered a disorder of neuroplasticity in brain reward and cognition systems resulting from aberrant activation of gene expression programs in response to prolonged drug consumption. Non-coding RNAs (ncRNAs) are key regulators of almost all aspects of cellular physiology. MicroRNAs (miRNAs) are small (~21-23 nucleotides) ncRNAs transcripts that regulate gene expression at the post-transcriptional level. Recently, miRNAs were shown to play key roles in the drug-induced remodeling of brain reward systems that likely drives the emergence of addiction. Here, we review evidence suggesting that one particular miRNA, miR-212, plays a particularly prominent role in vulnerability to cocaine addiction. We review evidence showing that miR-212 expression is increased in the dorsal striatum of rats that show compulsive-like cocaine-taking behaviors. Increases in miR-212 expression appear to protect against cocaine addiction, as virus-mediated striatal miR-212 overexpression decreases cocaine consumption in rats. Conversely, disruption of striatal miR-212 signaling using an antisense oligonucleotide increases cocaine intake. We also review data that identify two mechanisms by which miR-212 may regulate cocaine intake. First, miR-212 has been shown to amplify striatal cAMP response element binding protein (CREB) signaling through a mechanism involving activation of Raf1 kinase. Second, miR-212 was also shown to regulate cocaine intake by repressing striatal expression of methyl CpG binding protein 2 (MeCP2), consequently decreasing protein levels of brain-derived neurotrophic factor (BDNF). The concerted actions of miR-212 on striatal CREB and MeCP2/BDNF activity greatly attenuate the motivational effects of cocaine. These findings highlight the unique role for miRNAs in simultaneously controlling multiple signaling cascades implicated in addiction.

Original languageEnglish
Article numberArticle 43
JournalFrontiers in Genetics
Volume4
Issue numberMAY
DOIs
StatePublished - 2013
Externally publishedYes

Keywords

  • Cocaine
  • MeCP2
  • MiR-212
  • MiRNA

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