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Neural circuits of anxiolytic and antidepressant pherine molecules
CNS Spectrums ( IF 3.3 ) Pub Date : 2020-10-23 , DOI: 10.1017/s109285292000190x
Louis Monti 1 , Michael R Liebowitz 2, 3
Affiliation  

In this review, we describe proposed circuits mediating the mechanism of action of pherines, a new class of synthetic neuroactive steroids with demonstrated antianxiety and antidepressant properties, that engage nasal chemosensory receptors. We hypothesize that afferent signals triggered by activation of these peripheral receptors could reach subgroups of olfactory bulb neurons broadcasting information to gamma-aminobutyric acid (GABAergic) and corticotropin-releasing hormone (CRH) neurons in the limbic amygdala. We propose that chemosensory inputs triggered by pherines project to centrolateral (CeL) and centromedial (CeM) amygdala neurons, with downstream effects mediating behavioral actions. Anxiolytic pherines could activate the forward inhibitory GABAergic neurons that facilitate the release of neuropeptide S (NPS) in the locus coeruleus (LC) and GABA in the bed nucleus of the stria terminalis (BNST) and inhibit catecholamine release in the LC and ventral tegmental area (VTA) leading to rapid anxiolytic effect. Alternatively, antidepressant pherines could facilitate the CRH and GABAergic neurons that inhibit the release of NPS from the LC, increase glutamate release from the BNST, and increase norepinephrine (NE), dopamine (DA), and serotonin release from the LC, VTA, and raphe nucleus, respectively. Activation of these neural circuits leads to rapid antidepressant effect. The information provided is consistent with this model, but it should be noted that some steps on these pathways have not been demonstrated conclusively in the human brain.

中文翻译:

抗焦虑和抗抑郁的 pherine 分子的神经回路

在这篇综述中,我们描述了介导作用机制的拟议电路外星人,一类新的合成神经活性类固醇,具有抗焦虑和抗抑郁特性,可与鼻化学感觉受体结合。我们假设由这些外周受体激活触发的传入信号可以到达向 γ-氨基丁酸 (GABA) 广播信息的嗅球神经元亚群。精力充沛的) 和边缘杏仁核中的促肾上腺皮质激素释放激素 (CRH) 神经元。我们建议由 pherines 触发的化学感应输入投射到中央外侧 (CeL) 和中央内侧 (CeM) 杏仁核神经元,下游效应介导行为行为。抗焦虑的pherines可以激活前向抑制性GABA精力充沛的促进蓝斑 (LC) 中神经肽 S (NPS) 和终纹床核 (BNST) 中 GABA 释放并抑制 LC 和腹侧被盖区 (VTA) 中儿茶酚胺释放的神经元,导致快速抗焦虑作用. 或者,抗抑郁药 pherines 可以促进 CRH 和 GABA精力充沛的抑制 LC 释放 NPS、增加 BNST 释放谷氨酸、增加 LC、VTA 和中缝核释放去甲肾上腺素 (NE)、多巴胺 (DA) 和血清素的神经元。这些神经回路的激活会导致快速的抗抑郁作用。提供的信息与该模型一致,但应该注意的是,这些途径上的某些步骤尚未在人脑中得到最终证实。
更新日期:2020-10-23
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