Partial inhibition of catecholamine activity and enhanced responsiveness to NMDA after sustained administration of vortioxetine
Partial inhibition of catecholamine activity and enhanced responsiveness to NMDA after sustained administration of vortioxetine
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DOI：
10.1016/j.neuropharm.2017.10.036
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发表时间：
2018
影响因子：
4.7
通讯作者：
M. Ebrahimzadeh;M. Mansari;P. Blier
中科院分区：
文献类型：
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作者：
M. Ebrahimzadeh;M. Mansari;P. Blier
伏替西汀是一种多模式药物，可以阻断5-羟色胺(5-HT)的再摄取，并直接调节5-羟色胺受体。用细胞外单位记录和微离子电泳法研究了亚急性和长期给药对大鼠儿茶酚胺和谷氨酸系统各方面的影响。给药14天后，多巴胺(DA)神经元的放电频率显著降低(26%)，但不影响给药4天(含伏替西汀的饲料，1.8 mg/kg伏替西汀)。相同的伏替西汀给药14天和4天可降低去甲肾上腺素(NE)神经元的放电活动(分别减少27%和41%)。对于DA和NE神经元，伏替西汀暴露14天也减少了每分钟爆发的次数，但不改变每次爆发的棘波数目、爆发中的放电百分比和每个道的自发活动神经元的数目。然而，伏替西汀对多巴胺和去甲肾上腺素神经元活动的抑制作用弱于选择性5-羟色胺再摄取抑制剂(SSRI)艾司匹林。在海马CA3区，伏替西汀暴露14天并没有改变突触后α_2受体的敏感性，也没有增加α_1和α_2受体的紧张性激活。伏替西汀给药14d可增加N-甲基-d-天冬氨酸(N-甲基-d-aspartate，N-甲基-d-aspartate，N-甲基-d-天冬氨酸，α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic酸，AMPA)引起的锥体神经元反应。综上所述，目前的研究结果表明，与先前报道的艾司匹兰相比，伏替西汀对DA和NE神经元活动的抑制程度可能较小。
Vortioxetine is a multimodal drug that blocks serotonin (5-HT) reuptake and directly modulates 5-HT receptors. The effects of subacute and long-term administration of vortioxetine on various aspects of catecholamine and glutamate systems were investigated using single-unit extracellular recordings and microiontophoresis in the rat brain. The firing rate of dopamine (DA) neurons was significantly decreased (26%) after 14, but not 4 days of vortioxetine administration (vortioxetine-containing chow, 1.8 g/kg vortioxetine). Same 14- and 4-day regimens of vortioxetine decreased the firing activity of norepinephrine (NE) neurons (by 27% and 41%, respectively). For DA and NE neurons, 14-day vortioxetine exposure also decreased the number of bursts per minute, without changing the number of spikes per burst, percentage of spike firing in burst and the number of spontaneously active neurons per track. However, this vortioxetine-induced suppression of DA and NE neuronal activity is less than that obtained in previous studies with the selective 5-HT reuptake inhibitor (SSRI) escitalopram. In the CA3 region of the hippocampus, 14 days of vortioxetine exposure did not change the sensitivity of postsynaptic α2-adrenoceptors nor did it increase the tonic activation of α1-and α2-adrenoceptors. Vortioxetine administration for 14 days increased the N-methyl-d-aspartate (NMDA)-, but not α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-evoked responses of CA3 pyramidal neurons. Taken together, the results of the current study suggest that vortioxetine might produce a lesser inhibition of DA and NE neuronal activity when compared to those induced by escitalopram as reported in previous studies.