Document Detail

Activation of the ERK signalling pathway contributes to the adaptive changes in rat hearts during naloxone-induced morphine withdrawal.
MedLine Citation:
PMID:  17549049     Owner:  NLM     Status:  MEDLINE    
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.
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.
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.
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.
P Almela; M V Milanés; M L Laorden
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-04
Journal Detail:
Title:  British journal of pharmacology     Volume:  151     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-07-16     Completed Date:  2007-11-02     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  787-97     Citation Subset:  IM    
Department of Pharmacology, University School of Medicine, Murcia, Spain.
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MeSH Terms
Aminoacetonitrile / analogs & derivatives
Blotting, Western
Extracellular Signal-Regulated MAP Kinases / metabolism*
Gene Expression / drug effects
Genes, fos / drug effects
Heart Ventricles / drug effects
MAP Kinase Signaling System / drug effects
Morphine / adverse effects*
Naloxone / pharmacology*
Narcotic Antagonists / pharmacology*
Narcotics / adverse effects*
Phosphorylation / drug effects
Rats, Sprague-Dawley
Signal Transduction / drug effects
Substance Withdrawal Syndrome / metabolism*,  physiopathology
Reg. No./Substance:
0/Narcotic Antagonists; 0/Narcotics; 0/SL 327; 465-65-6/Naloxone; 540-61-4/Aminoacetonitrile; 57-27-2/Morphine; EC Signal-Regulated MAP Kinases

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