Effect of Methadone Maintenance on Expression of BDNF and CREB Genes in Brain VTA of Male Morphine Treated Rats.

Marzieh Rezai, Mohammad Reza Hajizadeh, Mehdi Mahmoodi, Seyedeh Atekeh Torabizadeh, Mojgan Noroozi Karimabad
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引用次数: 1

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.

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美沙酮维持对吗啡治疗雄性大鼠脑VTA BDNF和CREB基因表达的影响。
背景:吗啡可单独降低脑源性神经营养因子(BDNF)和循环amp反应元件结合蛋白(CREB)的表达水平。BDNF和CREB在保护和调节神经元正常功能中起着至关重要的作用。美沙酮维持治疗的效果及其与吗啡的比较研究尚未见报道。因此,本研究旨在探讨美沙酮维持对雄性吗啡治疗大鼠脑VTA中BDNF和CREB基因表达的影响。方法:取24只Wistar大鼠(200 ~ 250g)分为3个实验组:1)未给药动物(对照组);2)吗啡治疗动物(10 mg/kg, 2次/天,皮下注射,持续21天);3)吗啡治疗后美沙酮维持(14天内美沙酮维持剂量为第一周1 mg / 100 ml,第二周2.5 mg / 100 ml)。采用real - time PCR法评价BDNF和CREB基因的表达,实验结束时采用ELISA法测定血清BDNF蛋白水平。结果:本研究发现,与吗啡治疗组相似,吗啡治疗动物维持美沙酮可导致VTA处BDNF和CREB基因表达及血清BDNF水平较对照组显著降低。结论:美沙酮与吗啡一样,使大鼠脑VTA区BDNF、CREB基因表达及血清BDNF水平较对照组显著降低。
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来源期刊
Central nervous system agents in medicinal chemistry
Central nervous system agents in medicinal chemistry Psychology-Neuropsychology and Physiological Psychology
CiteScore
2.10
自引率
0.00%
发文量
21
期刊介绍: Central Nervous System Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new central nervous system agents. Containing a series of timely in-depth reviews written by leaders in the field covering a range of current topics, Central Nervous System Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in the field.
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