Abstract
BackgroundA great number of studies have investigated changes induced by morphine exposure in gene expression using several experimental models. In this study, we examined gene expression changes during chronic exposure to morphine during maturation and differentiation of zebrafish CNS.ResultsMicroarray analysis showed 254 genes whose expression was identified as different by at least 1.3 fold change following chronic morphine exposure as compared to controls. Of these, several novel genes (grb2, copb2, otpb, magi1b, grik-l, bnip4 and sox19b) have been detected for the first time in an experimental animal model treated with morphine. We have also identified a subset of genes (dao.1, wls, bnip4 and camk1γb) differentially expressed by chronic morphine exposure whose expression is related to mu opioid receptor gene expression. Altered expression of copb2, bnip4, sox19b, otpb, dao.1, grik-l and wls is indicative of modified neuronal development, CNS patterning processes, differentiation and dopaminergic neurotransmission, serotonergic signaling pathway, and glutamatergic neurotransmission. The deregulation of camk1γb signaling genes suggests an activation of axonogenesis and dendritogenesis.ConclusionsOur study identified different functional classes of genes and individual candidates involved in the mechanisms underlying susceptibility to morphine actions related to CNS development. These results open new lines to study the treatment of pain and the molecular mechanisms involved in addiction. We also found a set of zebrafish-specific morphine-induced genes, which may be putative targets in human models for addiction and pain processes.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-874) contains supplementary material, which is available to authorized users.
Highlights
A great number of studies have investigated changes induced by morphine exposure in gene expression using several experimental models
Microarrays analysis To examine the global transcriptional profiles of zebrafish embryos, RNAs generated from six pools of control zebrafish embryos and six pools of zebrafish embryos exposed to morphine were individually hybridized to Affymetrix Zebrafish Genome Arrays
We have described some genes whose expression is related to oprm1 expression: (i) Immediate early genes (IEG) and other genes related to transcription; (ii) genes involved in monoaminergic neuromodulation; (iii) genes involved in glutamatergic neurotransmission; and (iv) others genes involved in neuronal function
Summary
A great number of studies have investigated changes induced by morphine exposure in gene expression using several experimental models. Besides nonanalgesic uses of this drug, including experimental depression treatments as a control for opium addiction, has been developed [1,2]. Despite these common uses, morphine produces disruptive negative secondary effects including sleepiness, drowsiness, blurred vision, constipation, and a decrease in blood pressure and appetite. All microarray studies reporting gene expression changes in response to morphine have been conducted in rodents and humans These studies were performed in whole tissues (mainly brain), distinct components of the nervous system (nucleus accumbens, striatum, hippocampus, frontal cortex, spinal cord), or cell cultures (primary and cell lines)
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