Background and Objective: Morphine is a potent analgesic that is used to treat chronic pain but its utility is limited by the development of morphine tolerance. Several kinds of research have shown that calcium/calmodulin-dependent protein kinase IIα (CamKIIα) and protein kinase Cγ (PKCγ) have some roles in morphine tolerance. On the other hand, the prefrontal cortex (PFC) is the main site in processing morphine effects on the brain. Therefore, the aim of this study was to examine changes in gene expression of CamKIIα and PKCγ in the PFC after induction of morphine analgesic tolerance in rats. Method: We used two groups of male Wistar rats, which one group of them received saline (1 ml/kg) and the other group received morphine (10 mg/kg) twice daily for eight days. On day 8, morphine-induced analgesic tolerance was assessed using a hotplate test of analgesia. Then, the rats were decapitated and the PFC was dissected in each rat on an ice-chilled surface. Changes in the gene expression of CamKIIα and PKCγ were examined using a quantitative RT-PCR method. Result: The results showed that repeated use of morphine for 8 days induced analgesic tolerance. The results of the gene expression examination showed that the CamKIIα gene expression was significantly increased in the PFC. However, no significant change was observed for the PKCγ gene expression in the PFC. Conclusions: It can be concluded the CamKIIα but not PKCγ via association with NMDA receptors in the PFC may be involved in the induction of morphine analgesic tolerance.
