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- Title
Overexpression of miR-9 in the Nucleus Accumbens Increases Oxycodone Self-Administration.
- Authors
Mavrikaki, Maria; Anastasiadou, Eleni; Ozdemir, Recep A; Potter, David; Helmholz, Carolin; Slack, Frank J; Chartoff, Elena H
- 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.
- Subjects
NUCLEUS accumbens; DOPAMINE receptors; OXYCODONE; OPIOID abuse; NON-coding RNA; DRUGS of abuse; APPETITE stimulants; COCAINE
- Publication
International Journal of Neuropsychopharmacology, 2019, Vol 22, Issue 6, p383
- ISSN
1461-1457
- Publication type
Article
- DOI
10.1093/ijnp/pyz015