Introduction: Calcium/calmodulin-dependent protein kinase II (CaMKII) is highly expressed in the hippocampus, which has a pivotal role in reward-related memories and morphine dependence. Methods: In the present study, morphine tolerance was induced in male Wistar rats by 7 days repeated morphine injections once daily, and then gene expression profile of α-isoform of CaMKII (CaMKIIα) in the hippocampus was evaluated after discontinuation of morphine injection during 21 days of morphine withdrawal. Control groups received saline for 7 consecutive days. For gene expression study, the rat brains were removed and the hippocampus was dissected in separate groups on 1, 3, 7, 14, and 21 day(s) of morphine withdrawal. A semi-quantitative RT-PCR method was used for evaluating gene expression profile. Results: Tolerance to morphine was verified by a significant decrease in morphine analgesia in a hotplate test on day 8 (one day after the final repeated morphine injections). The results showed that gene expression of CaMKIIα at mRNA level on day 1, 3, 7, 14 and 21 of morphine withdrawal compared to saline control group was significantly altered. Post hoc Tukey’s test revealed that gene expression of CaMKIIα on day 14 was significantly increased. Conclusion: It can be concluded that expression of the CaMKIIα gene during repeated injections of morphine would be increased and continued until 14 days of withdrawal, and then settle at a new set point. Therefore, morphine abstinence animals may have a strong memory for morphine reward, at least partly, due to up-regulation of CaMKIIα in the hippocampus during 14 days of morphine withdrawal.
