氟西汀及其代谢产物诺氟西汀对海马 GABA 能传导的调节作用

Receptors Pub Date : 2024-01-04 DOI:10.3390/receptors3010001
E. Vázquez-Gómez, Andy Hernández-Abrego, Jassiel Mejía-Piedras, Jesús García-Colunga
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引用次数: 0

摘要

重度抑郁症与 GABA 能通路的功能障碍有关。有趣的是,在人类和动物抑郁症模型中,抗抑郁药氟西汀可改变 GABA 能神经递质。然而,诺氟西汀(氟西汀的主要代谢产物)对 GABA 能神经递质的影响尚未得到研究。因此,我们探讨了氟西汀和/或去氟西汀是否会调节GABA能神经递质,以及这些物质是否会与海马CA1放射层中间神经元的GABAA受体相互作用。为此,我们使用全细胞电流钳和电压钳技术记录了放射层中间神经元的发射曲线、GABA能自发抑制性突触后电流(sIPSCs)以及GABA扑通诱导的电流。我们根据神经元的高发射特征选择了这些神经元。我们发现,氟西汀和诺氟西汀(20 µM)都能显著降低sIPSCs的频率而不改变其振幅,并能降低GABA诱导电流的振幅。这些结果表明,氟西汀和诺氟西汀可减少与放射层中间神经元接触的神经元的 GABA 释放,并负向调节这些中间神经元的 GABAA 受体,从而导致它们失去抑制,这反过来又可能有助于增强对海马 CA1 锥体神经元的抑制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Regulation of Hippocampal GABAergic Transmission by Fluoxetine and Its Metabolite Norfluoxetine
Major depression is related to dysfunction of the GABAergic pathway. Interestingly, the antidepressant fluoxetine modifies GABAergic neurotransmission in human and animal models of depression. However, the effects of norfluoxetine (the main metabolite of fluoxetine) on GABAergic neurotransmission have not yet been studied. Therefore, we explored whether fluoxetine and/or norfluoxetine may regulate GABAergic transmission and whether these substances interact with GABAA receptors in hippocampal CA1 stratum radiatum interneurons. For these purposes, we recorded the firing profile, GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs), and currents induced by GABA puffs in stratum radiatum interneurons using both whole-cell current- and voltage-clamp techniques. Interneurons were selected according with their high firing profile. We found that both fluoxetine and norfluoxetine (at 20 µM) significantly decreased the frequency of sIPSCs without modifying their amplitude and decreased the amplitude of GABA-induced currents. These results indicate that fluoxetine and norfluoxetine decrease GABA release from neurons contacting stratum radiatum interneurons and negatively modulate GABAA receptors in these interneurons, resulting in their disinhibition, which in turn may contribute to increasing the inhibition of hippocampal CA1 pyramidal neurons.
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