Introduction: The prefrontal cortex is one of the main targets of the mesocorticolimbic dopaminergic system, which has an important role in reward related learning and addiction to the opioids. However, there are few studies examining the gene expression profile of the PFC under conditions of the repeated injections of morphine. We aimed to examine the expression of prodynorphin, mu-opioid receptors, and dopamine D1 and D5 receptors in the PFC after repeated administrations of morphine. Method: Two experimental male Wistar rats received a regimen of 8 days treatments of saline (1 ml/kg) or morphine (10 mg/kg) twice daily, and were examined for induction of morphine tolerance with a hotplate test on day 8 of the schedule. Then, the gene expressions of prodynorphin, mu-opioid receptor, and dopamine D1 and D5 receptors were evaluated by using a qPCR method. Student t-test was used to compare means of data. P<0.05 was used as the statistical significant level. Results: The results of the hotplate test revealed that the repeated injections of morphine for 8 days induced morphine tolerance. The results of the gene expression indicated that the gene expression of prodynorphin, mu-opioid receptor, and dopamine D1 receptor but not dopamine D5 receptor were significantly increased in the PFC of the morphine tolerant group compared to the saline-treated group. Conclusion: Morphine tolerance affects the gene expression of prodynorphin, mu-opioid receptors, and dopamine D1 receptors, which suggest that molecular mechanisms at the gene expression level in the PFC are involved in morphine addiction and tolerance.
