Background: Morphine independently reduces the expression level of Brain-derived Neurotrophic Factor (BDNF) and Cyclic-AMP Response Element Binding protein (CREB). BDNF and CREB play a vital role in protecting and regulating the proper functioning of neurons. There has not been any study on the effect of methadone maintenance treatment and its comparison with morphine. Therefore, this study was conducted to examine the effect of methadone maintenance on the expression of BDNF and CREB genes in brain VTA of male morphine treated rats. Methods: In this study, 24 Wistar rats (200-250g) were assigned to three experimental groups: 1) Animals without morphine treatment (control); 2) Morphine treated animals (10 mg/kg, twice/day through subcutaneous injection for 21 days); 3) Animals under methadone maintenance after treatment with morphine (maintenance dose of methadone was achieved during 14 days equal to 1 mg per 100 ml at the first week and 2.5 mg per 100 ml at second week). To evaluate the expression of BDNF and CREB genes, real time PCR method was used, and ELISA was applied to measure the serum level of BDNF protein at the end of the experiment. Results: According to the findings of this study, similar to morphine treated group, methadone maintenance in morphine treated animals led to a significant reduction in the expression of BDNF and CREB genes at VTA as well BDNF serum level compared with the control group. Conclusion: It was concluded that methadone, like morphine, causes a significant reduction in the expression of BDNF and CREB genes in the brain VTA area of rats as well as BDNF serum level compared with the control group.
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