Effect of chronic morphine administration on Ca2+/Calmodulin-Dependent protein kinase IIα activity in rat locus coeruleus and its possible role in morphine dependency

Introduction: The aim of this study was to assess the effect of Ca2+/calmodulin-dependent kinase IIα (CaMKIIα) inhibitor (KN-93) injection into the locus coeruleus (LC) on the modulation of withdrawal signs. We also sought to study the effect of chronic morphine administration on CaMKIIα activity in the rat LC. Methods: The research was based on behavioral and molecular studies. In the behavioral study, we cannulated the LC with stereotaxic surgery and after 7 days of recovery, injections of KN-93, KN-92 (inactive analogue of KN-93) or DMSO (vehicle) was performed. Morphine and saline were injected in control groups. In the molecular study, we assessed the amount of phosphorylated CaMKIIα (pCaMKIIα) protein expression in LC nucleus using western blot technique. Results: Behavioral study There was a significant difference in withdrawal signs between KN-93 and morphine dependent groups (P<0.05). No significant difference was observed between KN-92 and morphine dependent groups and also between DMSO and morphine dependent groups. Molecular study Morphine and control groups and also morphine and naloxone groups showed significant differences in the level of pCaMKIIα (P<0.05). There was no significant difference between control and naloxone groups. Conclusion: Chronic morphine administration can increase the amount of CaMKIIα activity in LC nucleus and inhibition of this enzyme can decrease some withdrawal signs in dependent rats.