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Activation of the ERK signalling pathway contributes to the adaptive changes in rat hearts during naloxone-induced morphine withdrawal.
- Source :
-
British journal of pharmacology [Br J Pharmacol] 2007 Jul; Vol. 151 (6), pp. 787-97. Date of Electronic Publication: 2007 Jun 04. - Publication Year :
- 2007
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Abstract
- Background and Purpose: We have previously demonstrated that morphine withdrawal induced hyperactivity of the heart by activation of noradrenergic pathways innervating the left and right ventricle, as evaluated by noradrenaline turnover and c-Fos expression. The extracellular signal-regulated kinase (ERK) has been implicated in drug addiction, but its role in activation of the heart during morphine dependence remains poorly understood. Here, we have looked for activation of ERK during morphine withdrawal and if this activation induced gene expression.<br />Experimental Approach: Dependence on morphine was induced by s.c. implantation of morphine pellets for 7 days. Morphine withdrawal was precipitated on day 8 by injection of naloxone (2 mg kg(-1), s.c.). ERK1/2, their phosphorylated forms and c-Fos were measured by western blotting and immunohistochemistry of cardiac tissue.<br />Key Results: Naloxone-induced morphine withdrawal activated ERK1/2 and increased c-Fos expression in cardiac tissues. c-Fos expression was blocked by SL327, a drug that prevents ERK activation.<br />Conclusions and Implications: These results indicate that signalling through the ERKs is necessary for morphine withdrawal-induced hyperactivity of the heart and suggest that this pathway may also be involved in activation of immediate-early genes in both cytosolic and nuclear effector mechanisms that have the potential to bring about long-term changes in the heart.
- Subjects :
- Aminoacetonitrile analogs & derivatives
Animals
Blotting, Western
Gene Expression drug effects
Genes, fos drug effects
Heart Ventricles drug effects
Immunohistochemistry
MAP Kinase Signaling System drug effects
Male
Phosphorylation drug effects
Rats
Rats, Sprague-Dawley
Signal Transduction drug effects
Substance Withdrawal Syndrome physiopathology
Extracellular Signal-Regulated MAP Kinases metabolism
Morphine adverse effects
Naloxone pharmacology
Narcotic Antagonists pharmacology
Narcotics adverse effects
Substance Withdrawal Syndrome metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0007-1188
- Volume :
- 151
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- British journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 17549049
- Full Text :
- https://doi.org/10.1038/sj.bjp.0707301