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- W1971295767 abstract "Molecular adaptations underlying drug seeking and relapse remain largely unknown. Studies highlight post-transcriptional modifications mediated by microRNAs (miRNAs) in addiction and other neurological disorders. We have previously shown that chronic cocaine suppresses miR-124 and let-7d and induces the expression of miR-181a in mesolimbic pathway. To further address the role and target gene regulation network of these miRNAs in vivo in cocaine addiction, we developed lentiviral vector (LV)-expressing miRNAs and their corresponding silencers for stable and regulatable miRNA expression. We tested in vivo miRNA gain and loss of function on cocaine-induced conditioned place preference (CPP) by localized LV-miRNA regulation in the nucleus accumbens (NAc). LV-miR-124 and let-7d expression in the NAc attenuates cocaine CPP, whereas LV-miR-181a enhances it. Silencing miRNAs by corresponding LV-miRNA silencers expressing perfect miRNA target sequences inversed this effect on cocaine CPP. Doxycycline treatment for switching off silencer expression abolished the observed behavioral changes. Behavioral changes mediated by LV-miRNA regulation resulted in dynamic alterations in transcription factors, receptors, and other effector genes involved in cocaine-induced plasticity. Our results describe a complex regulatory pathway mediated by miRNAs in cocaine-mediated neuronal adaptations." @default.
- W1971295767 created "2016-06-24" @default.
- W1971295767 creator A5010330116 @default.
- W1971295767 creator A5067189977 @default.
- W1971295767 date "2011-02-09" @default.
- W1971295767 modified "2023-10-02" @default.
- W1971295767 title "Regulation of MiR-124, Let-7d, and MiR-181a in the Accumbens Affects the Expression, Extinction, and Reinstatement of Cocaine-Induced Conditioned Place Preference" @default.
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- W1971295767 doi "https://doi.org/10.1038/npp.2010.250" @default.
- W1971295767 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3079833" @default.
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