Antidepressant effects of combination of brexpiprazole and fluoxetine on depression-like behavior and dendritic changes in mice after inflammation.
Antidepressant effects of combination of brexpiprazole and fluoxetine on depression-like behavior and dendritic changes in mice after inflammation.
复制标题
Brexprazole和氟西汀组合对抑郁样行为和炎症后小鼠的树突变化的抗抑郁药作用。
DOI：
10.1007/s00213-016-4483-7
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发表时间：
2017-02
影响因子：
3.4
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
低剂量的非典型抗精神病药物与选择性5-羟色胺再摄取抑制剂（SSRIs）联合使用，可促进难治性抑郁症患者快速发挥抗抑郁作用。布雷哌唑是一种新型的非典型抗精神病药物，已被用于治疗抑郁症。本研究旨在探讨布雷哌唑是否能增强SSRI氟西汀在抑郁症炎症模型中的抗抑郁作用。我们检测了氟西汀（10 mg/kg）、布雷哌唑（0.1 mg/kg）或两种药物联合给药对脂多糖（0.5 mg/kg）给药后抑郁样行为、脑源性神经营养因子（BDNF）- TrkB信号传导改变和选定脑区树突棘密度的影响。在炎症模型中，布雷哌唑和氟西汀的联合促进了快速的抗抑郁作用，尽管布雷哌唑或氟西汀单独没有显示出抗抑郁作用。此外，该组合显著改善了LPS诱导的前额叶皮层、CA 3和齿状回以及延髓核中的BDNF - TrkB信号传导和树突棘密度的改变。这些结果表明，在抑郁症的LPS炎症模型中，添加Brexpipazole至氟西汀可以产生快速的抗抑郁作用，表明Brexpipazole至SSRIs的连续治疗可以在伴有炎症的抑郁症患者中产生快速的抗抑郁作用。
Addition of low doses of atypical antipsychotic drugs with selective serotonin reuptake inhibitors (SSRIs) could promote a rapid antidepressant effect in treatment-resistant patients with major depression. Brexpiprazole, a new atypical antipsychotic drug, has been used as adjunctive therapy for the treatment of major depression. The present study was undertaken to examine whether brexpiprazole could augment antidepressant effects of the SSRI fluoxetine in an inflammation model of depression. We examined the effects of fluoxetine (10 mg/kg), brexpiprazole (0.1 mg/kg), or the combination of the two drugs on depression-like behavior, alterations in the brain-derived neurotrophic factor (BDNF) - TrkB signaling, and dendritic spine density in selected brain regions after administration of lipopolysaccharide (LPS) (0.5 mg/kg). Combination of brexpiprazole and fluoxetine promoted a rapid antidepressant effect in inflammation model although brexpipazole or fluoxetine alone did not show antidepressant effect. Furthermore, the combination significantly improved LPS-induced alterations in the BDNF - TrkB signaling and dendritic spine density in the prefrontal cortex, CA3 and dentate gyrus, and nucleus accumbens. These results suggest that add-on of brexpiprazole to fluoxetine can produce a rapid antidepressant effect in the LPS inflammation model of depression, indicating that adjunctive therapy of brexpiprazole to SSRIs could produce a rapid antidepressant effect in depressed patients with inflammation.