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چکیده
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Background and Objective: It is well known that chronic administrations of morphine results in the development of tolerance to its analgesic effects. Pharmacological data has shown not only changes in the mu-opioid receptors but also in the N-methyl-D-Aspartate (NMDA) receptors play an important role in the induction of morphine-induced analgesic tolerance. The MAP-Kinases are a specific class of serine/threonine kinases that respond to many extracellular signals. Recent studies show that MAP-kinases are involved in signaling pathways originating from the NMDA receptors. In this study, we aim to examine changes in the gene expression of the GluN1, as the main subunit of NMDA receptors and c-Jun N-terminal kinase (JNK3), as a member of MAP-kinases in the PFC in morphine-tolerant rats. Method: Two groups of male Wistar rats received saline (1 ml/kg) or morphine (10 mg/kg) twice daily for 8 days. Induction of morphine tolerance was assessed using the hotplate test of analgesia on day 8. Two hours after the last injections on day 8, each rat was anesthetized, decapitated and the PFC was dissected on an ice-chilled surface. The gene expression of the GluN1 and Jnk3 MAP-kinase was done using a real-time PCR method. Result: The results of the hotplate test of analgesia revealed that morphine treatment for 8 days induced analgesic tolerance. The results of the real-time PCR showed that the gene expression the GluN1 subunit of the NMDA receptor was significantly increased after morphine tolerance (P<0.01). In addition, according to the results of the real-time PCR, the gene expression of the Jnk3 MAP-kinase, similar to the GluN1, was significantly increased in the PFC. Conclusions: It can be concluded that morphine tolerance affects the gene expression of the NMDA receptor and the JNK3 MAP-kinase in the PFC, which may underlie at least partly, the molecular mechanism in the PFC that involved in the induction of morphine tolerance.
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