Role of PKC-alpha,gamma isoforms in regulation of c-Fos and TH expression after naloxone-induced morphine withdrawal in the hypothalamic PVN and medulla oblongata catecholaminergic cell groups
| Autor: | Marta, Benavides, M Luisa, Laorden, M Teresa, Marín, M Victoria, Milanés |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Neurons Medulla Oblongata Tyrosine 3-Monooxygenase Naloxone Blotting Western Cell Count Naphthalenes Rats Rats Sprague-Dawley Catecholamines Gene Expression Regulation Animals Protein Isoforms Drug Interactions Enzyme Inhibitors Morphine Dependence Proto-Oncogene Proteins c-fos Protein Kinase C Paraventricular Hypothalamic Nucleus |
| Zdroj: | Journal of neurochemistry. 95(5) |
| ISSN: | 0022-3042 |
| Popis: | We previously demonstrated that morphine withdrawal induced hyperactivity of the hypothalamus-pituitary-adrenocortical axis by activation of noradrenergic pathways innervating the hypothalamic paraventricular nucleus (PVN), as evaluated by Fos expression and corticosterone release. The present study was designed to investigate the role of protein kinase C (PKC) in this process by estimating changes in PKCalpha and PKCgamma immunoreactivity, and whether pharmacological inhibition of PKC would attenuate morphine withdrawal-induced c-Fos expression and changes in tyrosine hydroxylase (TH) immunoreactivity levels in the PVN and nucleus tractus solitarius/ ventrolateral medulla (NTS/VLM). Dependence on morphine was induced in rats by 7 day s.c. implantation of morphine pellets. Morphine withdrawal was induced on day 8 by an injection of naloxone. The protein levels of PKCalpha and gamma were significantly down-regulated in the PVN and NTS/VLM from the morphine-withdrawn rats. Morphine withdrawal induced c-Fos expression in the PVN and NTS/VLM, indicating an activation of neurons in those nuclei. TH immunoreactivity was increased in the NTS/VLM after induction of morphine withdrawal, whereas there was a decrease in TH levels in the PVN. Infusion of calphostin C, a selective protein kinase C inhibitor, produced a reduction in the morphine withdrawal-induced c-Fos expression. Additionally, the changes in TH levels in the PVN and NTS/VLM were significantly modified by calphostin C. The present results suggest that activated PKC in the PVN and catecholaminergic brainstem cell groups may be critical for the activation of the hypothalamic-pituitary adrenocortical axis in response to morphine withdrawal. |
| Databáze: | OpenAIRE |
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