title: Regulation of Pleiotrophin, Midkine, Receptor Protein Tyrosine Phosphatase β/ζ, and Their Intracellular Signaling Cascades in the Nucleus Accumbens During Opiate Administration.
abstract: BACKGROUND
  Most classes of addictive substances alter the function and structural plasticity of the brain reward circuitry. Midkine (MK) and pleiotrophin (PTN) are growth/differentiation cytokines which, similarly to neurotrophins, play an important role in repair, neurite outgrowth, and cell differentiation. PTN or MK signaling through receptor protein tyrosine phosphatase β/ζ (RPTPβ/ζ), leads to the activation of extracellular signal-regulated kinases and thymoma viral proto-oncogene. This activation induces morphological changes and modulates addictive behaviors. Besides, there is increasing evidence that during the development of drug addiction, astrocytes contribute to the synaptic plasticity by synthesizing and releasing substances such as cytokines.
  
  
  METHODS
  In the present work we studied the effect of acute morphine administration, chronic morphine administration, and morphine withdrawal on PTN, MK, and RPTPβ/ζ expression and on their signaling pathways in the nucleus accumbens.
  
  
  RESULTS
  Present results indicated that PTN, MK, and RPTPβ/ζ levels increased after acute morphine injection, returned to basal levels during chronic opioid treatment, and were up-regulated again during morphine withdrawal. We also observed an activation of astrocytes after acute morphine injection and during opiate dependence and withdrawal. In addition, immunofluorescence analysis revealed that PTN, but not MK, was overexpressed in astrocytes and that dopaminoceptive neurons expressed RPTPβ/ζ.
  
  
  CONCLUSIONS
  All these observations suggest that the neurotrophic and behavioral adaptations that occur during opiate addiction could be, at least partly, mediated by cytokines.
authors.affiliation: Group of Cellular and Molecular Pharmacology, University of Murcia, Campus de Espinardo, Murcia, Spain (Mr García-Pérez, Drs Laorden, and Milanés); IMIB, Instituto Murciano de Investigación Biosanitaria, Murcia, Spain (Mr García-Pérez, Drs Laorden, and Milanés). daniel.garcia9@um.es.
authors.forename: Daniel
authors.initials: D
authors.lastname: García-Pérez
authors.affiliation: Group of Cellular and Molecular Pharmacology, University of Murcia, Campus de Espinardo, Murcia, Spain (Mr García-Pérez, Drs Laorden, and Milanés); IMIB, Instituto Murciano de Investigación Biosanitaria, Murcia, Spain (Mr García-Pérez, Drs Laorden, and Milanés).
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Laorden
authors.affiliation: Group of Cellular and Molecular Pharmacology, University of Murcia, Campus de Espinardo, Murcia, Spain (Mr García-Pérez, Drs Laorden, and Milanés); IMIB, Instituto Murciano de Investigación Biosanitaria, Murcia, Spain (Mr García-Pérez, Drs Laorden, and Milanés).
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Milanés
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D000078792:Midkine; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D002352:Carrier Proteins; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D009292:Narcotic Antagonists; C066845:pleiotrophin; D000078792:Midkine; D009270:Naloxone; D009020:Morphine; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5
keywords: Astrocyte; glial fibrillary acidic protein; midkine; morphine; pleiotrophin; withdrawal