Distinct miRNA expression in dorsal striatal subregions is associated with risk for addiction in rats

R K Quinn; A. L. Brown; B. J. Goldie; E M Levi; P W Dickson; D W Smith; M. J. Cairns; C V Dayas

doi:10.1038/tp.2014.144

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Distinct miRNA expression in dorsal striatal subregions is associated with risk for addiction in rats

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Distinct miRNA expression in dorsal striatal subregions is associated with risk for addiction in rats

R K Quinn, A. L. Brown, B. J. Goldie, E M Levi, P W Dickson, D W Smith, M. J. Cairns and C V Dayas

Translational psychiatry, Vol.5, e503

03/02/2015

DOI: https://doi.org/10.1038/tp.2014.144

PMCID: PMC4445746

PMID: 25646592

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Life Sciences & Biomedicine

Psychiatry

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Neurosciences

Recently, we published data using an animal model that allowed us to characterize animals into two groups, addiction vulnerable and addiction resilient, where we identified that addiction/relapse vulnerability was associated with deficits in synaptic plasticity-associated gene expression in the dorsal striatum (DS). Notable was the strong reduction in expression for activity-regulated cytoskeleton-associated protein (Arc) considered a master regulator of synaptic plasticity. In the present study, we confirmed that Arc messenger RNA was significantly decreased in the DS, but importantly, we identified that this reduction was restricted to the dorsomedial (DMS) and not dorsolateral striatum (DLS). There is recent evidence of microRNA (miRNA)-associated posttranscriptional suppression of Arc and animal models of addiction have identified a key role for miRNA in the regulation of addiction-relevant genes. In further support of this link, we identified several differentially expressed miRNA with the potential to influence addiction-relevant plasticity genes, including Arc. A key study recently reported that miR-212 expression is protective against compulsive cocaine-seeking. Supporting this hypothesis, we found that miR-212 expression was significantly reduced in the DMS but not DLS of addiction-vulnerable animals. Together, our data provide strong evidence that miRNA promote ongoing plasticity deficits in the DS of addiction-vulnerable animals.

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Title: Distinct miRNA expression in dorsal striatal subregions is associated with risk for addiction in rats
Creators: R K Quinn - University of Newcastle Australia
A. L. Brown - University of Newcastle Australia
B. J. Goldie - University of Newcastle Australia
E M Levi - University of Newcastle Australia
P W Dickson - University of Newcastle Australia
D W Smith - University of Newcastle Australia
M. J. Cairns - University of Newcastle Australia
C V Dayas - University of Newcastle Australia
Publication Details: Translational psychiatry, Vol.5, e503
Publisher: Springer Nature
Grant note: These studies were supported by funding from the Australian National Health and Medical Research Council, the Hunter Medical Research Institute and the University of Newcastle through project grants to CVD.
Identifiers: 991013086313302368
Copyright: This work is licensed under a Creative Commons AttributionNonCommercial-NoDerivs 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/.)
Academic Unit: SCU College
Language: English
Resource Type: Journal article

Distinct miRNA expression in dorsal striatal subregions is associated with risk for addiction in rats

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