Background and Aim: Morphine is a widely used opioid analgesic but induction of morphine tolerance after its repeated injections has limited the use of the drug. Morphine binds selectively to the µ opioid receptors, which in turn activate protein kinase C (PKC) in its signaling pathway. PKC, especially its gamma isoform(PKCγ), is considered to play a key role in the development of morphine tolerance. The present study was performed to investigate the possible changes in gene expression of PKCγ in different times during induction of morphine tolerance in rat spinal cord. Methods: We used male Wistar rats in 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 assessed with a hotplate test during the schedule on days 1, 4 and 8 (one day after the last injection). For gene expression study, we used a semi-quantitative RT-PCR method to measure changes in gene expression of PKCγ at mRNA levels in other experimental groups including control and morphine-treated groups on days 4 and 8 after the injections. Results: Expression of PKCγ in morphine-treated group compared to the saline-treated control group on days 4 and 8 after injection was not significantly altered. However, expression of PKCγ in morphine-treated group on day 8 of the schedule compared to its expression in the group with day 4 morphine treatment was decreased. Conclusions: In can be concluded that expression of PKCγ during induction of morphine analgesic tolerance from day 1 until day 8 has been decreased and this decrease may account, at least partly, for its ineffectiveness or morphine-induced analgesic tolerance.
