PUBLICATION

Morphine regulates dopaminergic neuron differentiation via miR-133b

Authors
Sanchez-Simon, F.M., Zhang, X.X., Loh, H.H., Law, P.Y., and Rodriguez, R.E.
ID
ZDB-PUB-100820-26
Date
2010
Source
Molecular pharmacology   78(5): 935-942 (Journal)
Registered Authors
Rodriguez, Raquel E.
Keywords
MAP Kinase, Regulation of gene expression, Opioids
Datasets
GEO:GSE18847
MeSH Terms
  • Analgesics, Opioid/pharmacology*
  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Dopamine/metabolism*
  • Embryo, Nonmammalian
  • Enzyme Activation
  • Gene Expression Regulation
  • Gene Silencing
  • Hippocampus/cytology
  • Hippocampus/metabolism
  • MicroRNAs/biosynthesis
  • MicroRNAs/physiology*
  • Mitogen-Activated Protein Kinase 1/metabolism
  • Mitogen-Activated Protein Kinase 3/metabolism
  • Morphine/pharmacology*
  • Neurons/cytology
  • Neurons/drug effects*
  • Neurons/metabolism
  • Oligonucleotide Array Sequence Analysis
  • Rats
  • Receptors, Opioid, mu/genetics
  • Receptors, Opioid, mu/physiology
  • Signal Transduction
  • Zebrafish
PubMed
20716624 Full text @ Mol. Pharmacol.
Abstract
Morphine is one of the most used analgesics to treat chronic pain, although its long-term administration produces tolerance and dependence through neuronal plasticity. The ability of morphine to regulate neuron differentiation in vivo has been reported. However, the detailed mechanisms have not yet been elucidated due to the inability to separate maternal influences from the embryonic events. Using zebrafish embryos as the model, we demonstrate that morphine decreases miR-133b expression, hence increasing the expression of its target, Pitx3, a transcription factor that activates tyrosine hydroxylase (TH) and dopamine receptor 1 (DRD1). Using a specific morpholino to knock down the zfMOR in the embryos and selective MAPKinase inhibitors, we demonstrate that the morphine-induced miR-133b decrease in zebrafish embryos is mediated by zfMOR activation of ERK1/2. A parallel morphine-induced downregulation of miR-133b was observed in the immature but not in mature rat hipoccampal neurons. Our results point for the first time that zebrafish embryos express a functional mu opioid receptor, and that zebrafish serves as an excellent model to investigate the roles of miR in neuronal development affected by chronic morphine exposure.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping