Shamseddin Ahmadi - Department of Biological Science, Faculty of Science, University of Kurdistan, Sanandaj, Iran
Fatemeh Miraki - Department of Biological Science, Faculty of Science, University of Kurdistan, Sanandaj, Iran
Jalal Rostamzadeh - Department of Biological Science, Faculty of Science, University of Kurdistan, Sanandaj, Iran

Objective(s): We aimed to examine association of gene expression of MOR۱ and GluN۱ at mRNA level in the lumbosacral cord and midbrain with morphine tolerance in male Wistar rats. Materials and Methods: Analgesic effects of morphine administrated intraperitoneally at doses of ۰.۱, ۱, ۵ and ۱۰ mg/kg were examined using a hot plate test in rats with and without a history of ۱۵ days morphine (۱۰ mg/kg) treatment. Morphine-induced analgesic tolerance was also assessed on days ۱, ۵, ۱۰ and ۱۵ of chronic morphine injections. Two groups with history of ۱۵ days injections of saline or morphine (۱۰ mg/kg) were decapitated on day ۱۵ and their lumbosacral cord and midbrain were dissected for evaluating MOR۱ and GluN۱ gene expression. Results: The results of the hot plate test showed that morphine (۵ and ۱۰ mg/kg) induced significant analgesia in naïve rats but its analgesic effects in rats receiving ۱۵ days injections of morphine (۱۰ mg/kg) was decreased, indicating tolerance to morphine analgesia. The results also showed that the GluN۱ gene expression in tolerant rats was decreased by ۷۱ % in the lumbosacral cord but increased by ۱۱۰ % in the midbrain compared to the control group. However, no significant change was observed for the MOR۱ gene expression in both areas. Conclusion: It can be concluded that tolerance following administration of morphine (۱۰ mg/kg) for ۱۵ days is associated with site specific changes in the GluN۱ gene expression in the spinal cord and midbrain but the MOR۱ gene expression is not affected.

Analgesic tolerance, Gene expression, Mu-opioid receptor, NMDA receptor, Rat