شمس الدین احمدی

Background and Aim:Opiates are the most effective analgesics for treatment of moderate to severe pain. However, chronic administrations of opiates results in development of tolerance to their analgesic effects, which limits their use.Protein kinase C is a key molecule that pharmacological data has shown to play an important role in morphine-induced analgesictolerance. In this study, we aimed to examine changes in PKCγ gene expression in rat midbrain during induction of morphine tolerance. Methods: We used male Wistar rats in the experiments. Two experimental groups received morphine (10 mg/kg, i.p.) or saline (1 ml/kg, i.p.) twice a day for 7 days and induction of morphine analgesic tolerance was examined with a hotplate test during the injections schedule on days 1, 4 and 8 (one day after the last injection). Furthermore, two groups were received the same treatments and sacrificed on day 4. Two other groups were also received the same treatments and sacrificed on day 8 of the injections. Then, rat midbrain was immediately extracted to examine changes in gene expression of PKCγ during and after the induction of analgesic tolerance. A semi-quantitative RT-PCR method was used to examine changes in the amount of mRNA levels of PKCγ. Results:The results showed that gene expression of PKCγ in morphine-treated group compared to the saline-treated control group during induction of morphine analgesic tolerance on day 4 of repeated injections significantly increased but remained without significant difference compared to control group after induction of morphine tolerance on day 8 of the schedule. Conclusions: It can be concluded that changes in gene expression of PKCγ in rat midbrain during repeated injections may have an impact on induction of morphine analgesic tolerance. However, homeostasis processes may compensate changes in gene expression of PKCγ after induction of morphine analgesic tolerance. This result may also propose that other signaling molecule may have a rol