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Morphine regulates dopaminergic system via miR‐133b and Pitx3 in zebrafish embryos
Author(s) -
SanchezSimon Fatima Macho,
Zeng Yan,
Loh Horace H.,
Lae PingYee,
Rodriguez Raquel E.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.766.10
Subject(s) - dopaminergic , zebrafish , mapk/erk pathway , embryo , morphine , microrna , microbiology and biotechnology , chemistry , biology , medicine , pharmacology , endocrinology , dopamine , signal transduction , gene , biochemistry
Current studies were initiated to address whether morphine could affect neural development via its regulation of miRs. By microarray analysis, we show that morphine decreases miR‐133b expression. miR‐133b targets Pitx3, a transcription factor that activates genes involved in dopaminergic differentiation, such as TH and DRD1. Exposure of 24 hpf zebrafish embryos to morphine resulted in a decrease in miR‐133b and an increase in Pitx3, TH and DRD1 mRNA levels. Injection of the 3′UTR region of Pitx3 did not alter miRNA‐133b expression, and increased the expression of Pitx3, TH and DRD1. When ZfMOR (zebrafish mu opioid receptor) was silenced in embryos via morpholino injection, miR‐133b level increased and the expression of Pitx3 decreased. Parallel morphine regulation of miR‐133b level can be observed in primary neuron cultures from rat hippocampus. Embryo treatment with MAPK inhibitors U0126 or PD98059 increased miR‐133b level and decreased Pitx3 level. These studies suggest that the dopaminergic system development could be controlled by morphine‐mediated activation of ZfMOR. As the dopaminergic system is essential in the development of addiction, our findings contribute to the better understanding of the pathway that leads to addictive disorders. Research funded by the Spanish MEC (SAF2007‐61581) and the NIH, USA ( DA007339 ).