PMID- 23717324
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130530
LR  - 20211021
IS  - 1664-8021 (Print)
IS  - 1664-8021 (Electronic)
IS  - 1664-8021 (Linking)
VI  - 4
DP  - 2013
TI  - MicroRNAs and Drug Addiction.
PG  - 43
LID - 10.3389/fgene.2013.00043 [doi]
LID - 43
AB  - 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 ( approximately 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.
FAU - Bali, Purva
AU  - Bali P
AD  - Laboratory of Behavioral and Molecular Neuroscience, Department of Molecular 
      Therapeutics, The Scripps Research Institute - Florida Jupiter, FL, USA ; 
      Laboratory of Behavioral and Molecular Neuroscience, Department of Neuroscience, 
      The Scripps Research Institute - Florida Jupiter, FL, USA.
FAU - Kenny, Paul J
AU  - Kenny PJ
LA  - eng
GR  - R01 DA025983/DA/NIDA NIH HHS/United States
PT  - Journal Article
DEP - 20130510
PL  - Switzerland
TA  - Front Genet
JT  - Frontiers in genetics
JID - 101560621
PMC - PMC3650656
OTO - NOTNLM
OT  - MeCP2
OT  - cocaine
OT  - miR-212
OT  - miRNA
EDAT- 2013/05/30 06:00
MHDA- 2013/05/30 06:01
PMCR- 2013/05/10
CRDT- 2013/05/30 06:00
PHST- 2012/10/23 00:00 [received]
PHST- 2013/03/11 00:00 [accepted]
PHST- 2013/05/30 06:00 [entrez]
PHST- 2013/05/30 06:00 [pubmed]
PHST- 2013/05/30 06:01 [medline]
PHST- 2013/05/10 00:00 [pmc-release]
AID - 10.3389/fgene.2013.00043 [doi]
PST - epublish
SO  - Front Genet. 2013 May 10;4:43. doi: 10.3389/fgene.2013.00043. eCollection 2013.