Backgrounds: Molecular mechanisms involved in adverse effects of morphine, including tolerance and dependence have remained elusive. We examined possible alterations in the gene expression of proenkephalin (Penk), prodynorphin (Pdyn), and mu-opioid receptor (Oprm1) in reward brain areas following frequent morphine treatment. Methods: Two groups of male Wistar rats were used. The experimental groups received either saline (1ml/kg) or morphine (10 mg/kg) twice daily for eight days. On day 8, rats were decapitated, brain areas involved in addiction, including the midbrain, striatum, prefrontal cortex (PFC), hippocampus, and hypothalamus were dissected, and gene expression was evaluated with real-time PCR. Results: The results revealed that prolonged morphine treatment decreased the Penk, Pdyn, and Oprm1 gene expression in the midbrain but upregulated them in the striatum compared to the control group treated with saline. Significant increases in the Pdyn and Oprm1 gene expression were detected in the PFC but there was no significant change in the Penk gene expression between the two examined groups. The Pdyn gene expression decreased in the hippocampus and hypothalamus; however, no significant alterations in the Penk and Oprm1 gene expression were detected between the experimental groups in these areas. Conclusion: It can be concluded the expression of endogenous opioid peptides and receptors after frequent use of morphine follows a region specificity in the brain areas involved in addiction. These alterations may result in new physiological setpoints outside the normal range, which need to be considered in using morphine in medicine.
