Background and Aim: Morphine is widely used to treat chronic pain but its utility is hindered by the development of tolerance to its analgesic effects.Pharmacological data have shown that calcium/calmodulin-dependent protein kinase IIα (CamKIIα) is involved in morphine-induced analgesic tolerance.The aim of this study was to examine changes in gene expression of CamKIIα during and after induction of morphine analgesic tolerance. Methods: We used male Wistar rats weighing 280-320g in these experiments. Two groups of rats (n= 8) received saline 1 ml/kg or morphine 10 mg/kgtwice daily for a schedule of 7 days. Morphine induced analgesic tolerance was assessed usinga hotplate test on days 1, 4 and 8 (one day after the last injection). Rat midbrain was also extracted in separate experimental groups on days 4 and 8 of the schedule.Change in gene expression of CamKIIα was examined with a semi-quantitative RT-PCR method. Results: First, the result of hotplate test showed that repeated injections of morphine induced analgesictolerance on day 8 but there was also a significant decrease in morphine analgesia on day 4 of the schedule. Second, the result of gene expression for CamKIIα in rat midbrain on day 4 showed an increase but it significantly decreased on day 8 after induction of morphine analgesic tolerance. Conclusion: It can be concluded that changes in gene expression of CamKIIα in rat midbrain may underlie morphine-induced analgesic tolerance.
