Cross-Talk between Protein Kinase A and Mitogen-Activated Protein Kinases Signalling in the Adaptive Changes Observed during Morphine Withdrawal in the Heart

Our previous studies have shown that morphine withdrawal induced an increase in the expression of protein kinase (PK) A and mitogen-activated extracellular kinase (MAPK) pathways in the heart during morphine withdrawal. The purpose of the present study was to evaluate the interaction between PKA and extracellular signal-regulated kinase (ERK) signaling pathways mediating the cardiac adaptive changes observed after nalox-one administration to morphine-dependent rats. Dependence on morphine was induced by a 7-day subcutaneous implanta-tion of morphine pellets. Morphine withdrawal was precipitated on day 8 by an injection of naloxone (2 mg/kg). ERK1/2 and tyrosine hydroxylase (TH) phosphorylation was determined by quantitative blot immunolabeling using phosphorylation state-specific antibodies. Naloxone-induced morphine withdrawa