Vortioxetine disinhibits pyramidal cell function and enhances synaptic plasticity in the rat hippocampus.
Vortioxetine disinhibits pyramidal cell function and enhances synaptic plasticity in the rat hippocampus.
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DOI：
10.1177/0269881114543719
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Sanchez C
中科院分区：
文献类型：
--
作者：
Dale E;Zhang H;Leiser SC;Xiao Y;Lu D;Yang CR;Plath N;Sanchez C
沃替西汀是一种新型多模式抗抑郁药，是5-羟色胺（5-HT）3、5-HT 7和5-HT 1D受体拮抗剂，5-HT 1B受体部分激动剂，5-HT 1A受体激动剂和5-HT转运体（SERT）抑制剂。沃替西汀已被证明可以改善几种临床前大鼠模型和重度抑郁症患者的认知能力。在这里，我们研究了这些影响的机制基础，通过研究沃替西汀对突触传递，长时程增强（LTP），学习和记忆的细胞相关性，以及在大鼠海马和额叶皮层的θ振荡的影响。发现沃替西汀防止5-HT诱导的从CA 1锥体细胞记录的抑制性突触后电位的增加，最有可能是通过5-HT 3受体拮抗作用。沃替西汀还增强海马CA 1区的LTP。最后，沃替西汀增加额皮质θ功率在整个动物脑电图记录活跃清醒。相比之下，选择性SERT抑制剂艾司西酞普兰对这些指标均无影响。总之，我们的结果表明，沃替西汀可以增加锥体细胞输出，这导致海马突触可塑性增强。鉴于海马在认知中的中心作用，这些发现可能为观察到的沃替西汀的临床前和临床认知增强作用提供细胞相关性。
Vortioxetine, a novel antidepressant with multimodal action, is a serotonin (5-HT)3, 5-HT7 and 5-HT1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist and a 5-HT transporter (SERT) inhibitor. Vortioxetine has been shown to improve cognitive performance in several preclinical rat models and in patients with major depressive disorder. Here we investigated the mechanistic basis for these effects by studying the effect of vortioxetine on synaptic transmission, long-term potentiation (LTP), a cellular correlate of learning and memory, and theta oscillations in the rat hippocampus and frontal cortex. Vortioxetine was found to prevent the 5-HT-induced increase in inhibitory post-synaptic potentials recorded from CA1 pyramidal cells, most likely by 5-HT3 receptor antagonism. Vortioxetine also enhanced LTP in the CA1 region of the hippocampus. Finally, vortioxetine increased fronto-cortical theta power during active wake in whole animal electroencephalographic recordings. In comparison, the selective SERT inhibitor escitalopram showed no effect on any of these measures. Taken together, our results indicate that vortioxetine can increase pyramidal cell output, which leads to enhanced synaptic plasticity in the hippocampus. Given the central role of the hippocampus in cognition, these findings may provide a cellular correlate to the observed preclinical and clinical cognition-enhancing effects of vortioxetine.
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影响因子：
3
作者：
Bastlund, JF;Jennum, P;Watson, WP
通讯作者：
Watson, WP
影响因子：
3
作者：
Basar, E;Basar-Eroglu, C;Schürmann, M
通讯作者：
Schürmann, M
DOI：
10.1017/s1461145711001027
发表时间：
2012-06
期刊：
The international journal of neuropsychopharmacology
影响因子：
--
作者：
Alvarez E;Perez V;Dragheim M;Loft H;Artigas F
通讯作者：
Artigas F
影响因子：
2.9
作者：
ARAI, A;LYNCH, G
通讯作者：
LYNCH, G
影响因子：
4.2
作者：
Arnsten, AFT;Lin, CH;Stanhope, KJ
通讯作者：
Stanhope, KJ