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Acute Morphine, Chronic Morphine, and Morphine Withdrawal Differently Affect Pleiotrophin, Midkine, and Receptor Protein Tyrosine Phosphatase β/ζ Regulation in the Ventral Tegmental Area.
- Source :
-
Molecular neurobiology [Mol Neurobiol] 2017 Jan; Vol. 54 (1), pp. 495-510. Date of Electronic Publication: 2016 Jan 07. - Publication Year :
- 2017
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Abstract
- Pleiotrophin (PTN) and midkine (MK) are secreted growth factors and cytokines, proposed to be significant neuromodulators with multiple neuronal functions. PTN and MK are generally related with cell proliferation, growth, and differentiation by acting through different receptors. PTN or MK, signaling through receptor protein tyrosine phosphatase β/ζ (RPTPβ/ζ), lead to the activation of extracellular signal-regulated kinases (ERKs) and thymoma viral proto-oncogene (Akt), which induce morphological changes and modulate 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. In the present work, we studied the effect of acute morphine, chronic morphine, and morphine withdrawal on PTN, MK, and RPTPβ/ζ expression and on their signaling pathways in the ventral tegmental area (VTA). 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 upregulated 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 dopaminergic neurons expressed RPTPβ/ζ. Interestingly, p-ERK 1/2 levels during chronic morphine and morphine withdrawal correlated RPTPβ/ζ expression. All these observations suggest that the neuroprotective and behavioral adaptations that occur during opiate addiction could be, at least partly, mediated by these cytokines.
- Subjects :
- Animals
Drug Administration Schedule
Male
Midkine
Morphine adverse effects
Rats
Rats, Wistar
Ventral Tegmental Area drug effects
Carrier Proteins biosynthesis
Cytokines biosynthesis
Morphine administration & dosage
Receptor-Like Protein Tyrosine Phosphatases, Class 5 biosynthesis
Substance Withdrawal Syndrome metabolism
Ventral Tegmental Area metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1182
- Volume :
- 54
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 26742526
- Full Text :
- https://doi.org/10.1007/s12035-015-9631-2