Background and Aim: Development of opioid-induced analgesic tolerance often led to their effectiveness limiting. Opioid drugs such as morphine bind selectively to the µ opioid receptors. In addition, calcium/calmodulin-dependent protein kinase IIα (CamKIIα) has been shown to be involved in regulation of opioid receptor signaling. Methods: We injected morphine 10 mg/kg (i.p.) twice daily for 7 days to induce morphine analgesic tolerance in male Wistar rats (250-300g). Two groups of rats received saline 1 ml/kg or morphine 10 mg/kgtwice daily for 7 days. Morphine induced analgesic tolerance was investigated using hotplate test on days 1, 4 and 8 (one day after the last injections) of the injections schedule.For gene expression study, the lumbosacral portion of the spinal cord wasalso extracted in separate saline or morphine treated groups on days 4 and 8 of the schedule to examine changes in gene expression of CamKIIα using a semi-quantitative RT-PCR method. Results: The result of hotplate test on day 8 of the schedule showed that morphine injectionstwice daily for 7 days compared tothe saline treated group lead to morphine-induced analgesictolerance, however, there was also a significant decrease in morphine analgesia on day 4 of the injections. The result of gene expression for CamKIIαin the spinal cord on day 4 of the injections of morphine was significantly increased but on day 8 of the schedule no significant increase was observed. Conclusion: It can be concluded that changes in gene expression of CamKIIα in the spinal cord during repeated injections of morphine may underlie induction of morphine analgesic tolerance.
