Title:Effect of Methadone Maintenance on Expression of BDNF and CREB Genes in Brain VTA of Male Morphine Treated Rats
Volume: 21
Issue: 3
Author(s): Marzieh Rezai, Mohammad Reza Hajizadeh, Mehdi Mahmoodi, Seyedeh Atekeh Torabizadeh and Mojgan Noroozi Karimabad*
Affiliation:
- Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan,Iran
Keywords:
Morphine, BDNF, CREB, methadone, VTA, drug overuse.
Abstract: 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.