Metabolic Brain Disease

, Volume 33, Issue 5, pp 1501–1508 | Cite as

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

  • Dan-Ni Cao
  • Jing-Jing Shi
  • Ning WuEmail author
  • Jin LiEmail author
Original Article


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.


miR-139-5p cAMP overshoot c-Jun morphine dependence and addiction 



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).

Compliance with ethical standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical CountermeasuresBeijing Institute of Pharmacology and ToxicologyBeijingChina

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