Adjunctive treatment of brexpiprazole with fluoxetine shows a rapid antidepressant effect in social defeat stress model: Role of BDNF-TrkB signaling.
Adjunctive treatment of brexpiprazole with fluoxetine shows a rapid antidepressant effect in social defeat stress model: Role of BDNF-TrkB signaling.
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DOI：
10.1038/srep39209
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发表时间：
2016-12-19
影响因子：
4.6
通讯作者：
Hashimoto K
中科院分区：
文献类型：
--
作者：
Ma M;Ren Q;Yang C;Zhang JC;Yao W;Dong C;Ohgi Y;Futamura T;Hashimoto K
添加低剂量的非典型抗精神病药物brexpipazole与选择性5-羟色胺再摄取抑制剂（SSRIs）可以促进抑郁症患者的抗抑郁作用，尽管联合用药的确切机制尚不清楚。在社交失败应激模型中，低剂量布雷哌唑（0.1mg/kg）和SSRI氟西汀（10 mg/kg）联合应用可促进快速的抗抑郁作用，而单独使用布雷哌唑或氟西汀则无抗抑郁作用。此外，该组合显着改善了社交失败压力后易感小鼠前额叶皮层，海马和延髓核中脑源性神经营养因子（BDNF）- TrkB信号传导和树突棘密度的变化。有趣的是，TrkB拮抗剂ANA-12显著阻断了布雷哌唑和氟西汀的组合对抑郁样表型的有益作用。这些结果表明，BDNF-TrkB信号传导在布雷哌唑和氟西汀的组合的快速抗抑郁作用中起作用。
Addition of low doses of the atypical antipsychotic drug brexpiprazole with selective serotonin reuptake inhibitors (SSRIs) could promote antidepressant effect in patients with major depressive disorder although the precise mechanisms underlying the action of the combination are unknown. Combination of low dose of brexpiprazole (0.1 mg/kg) and SSRI fluoxetine (10 mg/kg) could promote a rapid antidepressant effect in social defeat stress model although brexpiprazole or fluoxetine alone did not show antidepressant effect. Furthermore, the combination significantly improved alterations in the brain-derived neurotrophic factor (BDNF) - TrkB signaling and dendritic spine density in the prefrontal cortex, hippocampus, and nucleus accumbens in the susceptible mice after social defeat stress. Interestingly, TrkB antagonist ANA-12 significantly blocked beneficial effects of combination of brexpiprazole and fluoxetine on depression-like phenotype. These results suggest that BDNF-TrkB signaling plays a role in the rapid antidepressant action of the combination of brexpiprazole and fluoxetine.
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影响因子：
64.8
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作者：
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