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Regulation of extracellular signal-regulated kinases (ERKs) by naloxone-induced morphine withdrawal in the brain stress system.
- Source :
-
Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2008 Oct; Vol. 378 (4), pp. 407-20. Date of Electronic Publication: 2008 Jun 12. - Publication Year :
- 2008
-
Abstract
- Our previous studies have shown that morphine withdrawal increases the hypothalamic-pituitary-adrenocortical axis activity, which is dependent on a hyperactivity of noradrenergic pathways (nucleus tractus solitarius-A(2)) innervating the hypothalamic paraventricular nucleus. The extracellular signal-regulated kinase has been implicated in drug addiction, but its role in activation of paraventricular nucleus and nucleus tractus solitarius during morphine dependence remain poorly understood. We have determined the activation of extracellular signal-regulated kinase during morphine dependence and withdrawal as well as its involvement in morphine withdrawal-induced gene expression. We show that naloxone-induced morphine withdrawal activates extracellular signal-regulated kinases(1/2) and increases c-Fos expression in rat paraventricular nucleus and nucleus tractus solitarius-A(2) neurons. Activated extracellular signal-regulated kinases(1/2) was colocalized with c-Fos in both nuclei, and this response was blocked by SL327, a drug that prevents extracellular signal-regulated kinase activation. In the paraventricular nucleus from morphine-withdrawn rats, the number of neurons expressing CRF was increased. Immunohistochemical study showed a dramatic increase in c-Fos immunoreactivity within CRF-positive cells. These results suggest that extracellular signal-regulated kinases1/2 signaling pathway is necessary for morphine withdrawal-induced activation of brain areas associated with the stress system.
- Subjects :
- Aminoacetonitrile administration & dosage
Aminoacetonitrile analogs & derivatives
Aminoacetonitrile pharmacology
Animals
Blotting, Western
Brain metabolism
Brain pathology
Corticotropin-Releasing Hormone metabolism
Extracellular Signal-Regulated MAP Kinases antagonists & inhibitors
Immunochemistry
Injections, Subcutaneous
Male
Morphine administration & dosage
Morphine Dependence etiology
Morphine Dependence physiopathology
Naloxone administration & dosage
Narcotic Antagonists administration & dosage
Narcotic Antagonists pharmacology
Narcotics administration & dosage
Narcotics toxicity
Paraventricular Hypothalamic Nucleus drug effects
Paraventricular Hypothalamic Nucleus metabolism
Paraventricular Hypothalamic Nucleus pathology
Protease Inhibitors administration & dosage
Protease Inhibitors pharmacology
Proto-Oncogene Proteins c-fos metabolism
Rats
Rats, Sprague-Dawley
Signal Transduction drug effects
Solitary Nucleus drug effects
Solitary Nucleus metabolism
Solitary Nucleus pathology
Substance Withdrawal Syndrome etiology
Time Factors
Brain drug effects
Extracellular Signal-Regulated MAP Kinases metabolism
Morphine toxicity
Naloxone pharmacology
Substance Withdrawal Syndrome physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 0028-1298
- Volume :
- 378
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Naunyn-Schmiedeberg's archives of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 18548233
- Full Text :
- https://doi.org/10.1007/s00210-008-0304-9