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Modulation of miR-139-5p on chronic morphine-induced, naloxone-precipitated cAMP overshoot in vitro

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Abstract

Chronic exposure to morphine can produce tolerance, dependence and addiction, but the underlying neurobiological basis is still incompletely understood. c-Jun, as an important component of the activator protein-1 transcription factor, is supposed to take part in regulating gene expression in AC/cAMP/PKA signaling. MicroRNA (miRNA) has emerged as a critical regulator of neuronal functions. Although a number of miRNAs have been reported to regulate the μ-opioid receptor expression, there has been no report about miRNAs to regulate chronic morphine-induced, naloxone-precipitated cAMP overshoot. Our results showed that chronic morphine pretreatment induced naloxone-precipitated cAMP overshoot in concentration- and time-dependent manners in HEK 293/μ cells. Chronic morphine pretreatment alone elevated both c-Jun protein and miR-139-5p expression levels, while dramatically artificial elevation of miR-139-5p inhibited c-Jun at the translational level. Furthermore, dramatically artificial upregulation of intracellular miR-139-5p limited chronic morphine-induced, naloxone-precipitated cAMP overshoot. These findings suggested that miR-139-5p was involved in regulating chronic morphine-induced, naloxone-precipitated cAMP overshoot in a negative feedback manner through its target c-Jun, which extends our understanding of neurobiological mechanisms underlying morphine dependence and addiction.

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Acknowledgements

This work was supported by the National Basic Research Program of China (2015CB553504), National Key R&D Program of China (2017YFC1310404) and the National Natural Science Foundation of China (Nos. 81571302 and U1502225).

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Authors and Affiliations

  1. Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27th Taiping Road, Beijing, 100850, China

    Dan-Ni Cao, Jing-Jing Shi, Ning Wu & Jin Li

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  1. Dan-Ni Cao
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  2. Jing-Jing Shi
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  3. Ning Wu
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  4. Jin Li
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Correspondence to Ning Wu or Jin Li.

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Cao, DN., Shi, JJ., Wu, N. et al. Modulation of miR-139-5p on chronic morphine-induced, naloxone-precipitated cAMP overshoot in vitro. Metab Brain Dis 33, 1501–1508 (2018). https://doi.org/10.1007/s11011-018-0257-8

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