title: Whole-genome expression profile in zebrafish embryos after chronic exposure to morphine: identification of new genes associated with neuronal function and mu opioid receptor expression.
abstract: BACKGROUND
  A 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.
  
  
  RESULTS
  Microarray 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.
  
  
  CONCLUSIONS
  Our 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.
authors.forename: M Javier
authors.initials: MJ
authors.lastname: Herrero-Turrión
authors.forename: Iván
authors.initials: I
authors.lastname: Rodríguez-Martín
authors.forename: Roger
authors.initials: R
authors.lastname: López-Bellido
authors.affiliation: Instituto de Neurociencias de Castilla y León, University of Salamanca, Salamanca 37007, Spain. requelmi@usal.es.
authors.forename: Raquel E
authors.initials: RE
authors.lastname: Rodríguez
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002823:Chorion / Q000187:drug effects*; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000187:drug effects; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D009020:Morphine / Q000009:adverse effects*; D009474:Neurons / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017450:Receptors, Opioid, mu / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology*
chemical_list: D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D009020:Morphine