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.
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.
Authors: Cristina Mazzucchelli; Chiara Vantaggiato; Alessandro Ciamei; Stefania Fasano; Pavel Pakhotin; Wojciech Krezel; Hans Welzl; David P Wolfer; Gilles Pagès; Olga Valverde; Anne Marowsky; Annamaria Porrazzo; Paul C Orban; Rafael Maldonado; Markus U Ehrengruber; Vincenzo Cestari; Hans-Peter Lipp; Paul F Chapman; Jacques Pouysségur; Riccardo Brambilla Journal: Neuron Date: 2002-05-30 Impact factor: 17.173
Authors: Rebecca S Hofford; Stephen R Hodgson; Kris W Roberts; Camron D Bryant; Christopher J Evans; Shoshana Eitan Journal: Behav Pharmacol Date: 2009-10 Impact factor: 2.293
Authors: Sydney X Lu; Onder Alpdogan; Janine Lin; Robert Balderas; Roberto Campos-Gonzalez; Xiao Wang; Guo-Jian Gao; David Suh; Christopher King; Melanie Chow; Odette M Smith; Vanessa M Hubbard; Johanne L Bautista; Javier Cabrera-Perez; Johannes L Zakrzewski; Adam A Kochman; Andrew Chow; Gregoire Altan-Bonnet; Marcel R M van den Brink Journal: Blood Date: 2008-10-06 Impact factor: 22.113