Introduction: The mesocorticolimbic dopaminergic system from the midbrain to the nucleus accumbens, striatum, aymgdala and prefrontal cortex (PFC) has a pivotal role in reward related learning and addiction to the opioids. A significant amount of evidence also indicates that microRNAs (miRNAs) play an important role in drug addiction. However, few studies have examined the expression of miRNAs in the PFC under conditions of chronic morphine treatments. In his study, we aim to examine the expression of miRNAs including Let7C1, mir133b and mir365b in the PFC after repeated administrations of morphine. Materials and Methods: Two experimental male Wistar rats received a regimen of 8 days treatments of saline (1 ml/kg) or morphine (10 mg/kg) twice daily. The analgesic tolerance to the repeated injections of morphine was assessed with a hotplate apparatus on day 8 of the schedule. Then, the expressions of miRNAs including Let7C1, mir133b and mir365b were evaluated by using a qPCR method. Results: Hotplate test of analgesia confirmed the induction of morphine tolerance after 8 days of the repeated injections. The qPCR results revealed that the expression of Let7C1, mir133b and mir365b in morphine tolerant group were significantly increased compared to the saline-treated group. Conclusion: We conclude that the increases in the expression of miRNAs including Let7C1, mir133b and mir365b are involved in changes in the gene expressions in the PFC underlying morphine addiction and tolerance.
