1. Overexpression of miR-9 in the Nucleus Accumbens Increases Oxycodone Self-Administration.
- Author
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Mavrikaki M, Anastasiadou E, Ozdemir RA, Potter D, Helmholz C, Slack FJ, and Chartoff EH
- Subjects
- Animals, Behavior, Addictive chemically induced, Dependovirus genetics, Genetic Vectors administration & dosage, Male, Microinjections, Rats, Receptors, Dopamine D2 biosynthesis, Repressor Proteins biosynthesis, Self Administration, Behavior, Addictive physiopathology, MicroRNAs biosynthesis, MicroRNAs physiology, Nucleus Accumbens metabolism, Oxycodone pharmacology
- Abstract
Background: There is an urgent need to identify factors that increase vulnerability to opioid addiction to help stem the opioid epidemic and develop more efficient pharmacotherapeutics. MicroRNAs are small non-coding RNAs that regulate gene expression at a posttranscriptional level and have been implicated in chronic drug-taking in humans and in rodent models. Recent evidence has shown that chronic opioid treatment regulates the microRNA miR-9. The present study was designed to test the hypothesis that miR-9 in the nucleus accumbens potentiates oxycodone addictive-like behavior., Methods: We utilized adeno-associated virus (AAV) to overexpress miR-9 in the nucleus accumbens of male rats and tested the effects on intravenous self-administration of the highly abused prescription opioid, oxycodone, in 1-hour short-access followed by 6-h long-access sessions, the latter of which leads to escalation of drug intake. In separate rats, we assessed the effects of nucleus accumbens miR-9 overexpression on mRNA targets including RE1-silencing transcription factor (REST) and dopamine D2 receptor (DRD2), which have been shown to be regulated by drugs of abuse., Results: Overexpression of miR-9 in the nucleus accumbens significantly increased oxycodone self-administration compared with rats expressing a control, scrambled microRNA. Analysis of the pattern of oxycodone intake revealed that miR-9 overexpression increased "burst" episodes of intake and decreased the inter-infusion interval. Furthermore, miR-9 overexpression decreased the expression of REST and increased DRD2 in the nucleus accumbens at time points that coincided with behavioral effects., Conclusions: These results suggest that nucleus accumbens miR-9 regulates oxycodone addictive-like behavior as well as the expression of genes that are involved in drug addiction., (© The Author(s) 2019. Published by Oxford University Press on behalf of CINP.)
- Published
- 2019
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