About 16% of the world's population has major depressive disorder. Traditional antidepressants have slow effect rates and low response rates. Many studies have shown that low doses of ketamine can produce rapid and effective antidepressant effects. However, its mechanism of action needs further exploration. Lipopolysaccharide (LPS) was used to establish a depression model in rats and PC12 nerve cells were used for in vitro experiments. (2,4)-Dimethoxybenzylidene anabaseine dihydrochloride (GTS-21), a specific agonist of α7 nicotinic acetylcholine receptors (α7 nAChRs), was used to compare the rapid antidepressant effect of ketamine. Different doses of α7 nAChR antagonist methyllycaconatine (MLA) and α7 nAChR-siRNA were used to interfere with the protective effects of ketamine on neuroinflammation in rats and PC12 cells, respectively. MLA intervention downregulated the anti-inflammatory effects of ketamine and decreased the effects of ketamine on behavior, synaptic plasticity, and Nissl bodies in the neuronal cells. Moreover, the dose of MLA was positively correlated with the inhibitory effect in rat hippocampi and the protective effects of GTS-21 were consistent with ketamine. These results demonstrated that low-dose ketamine could produce neuroprotective effects by activating the α7 nAChR-mediated cholinergic anti-inflammatory pathway (CAP) in depression, resulting in a rapid antidepressant effect.

中文翻译：

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低剂量氯胺酮通过激活胆碱能抗炎途径改善了LPS诱导的大鼠抑郁样行为。

世界人口中约16％患有严重的抑郁症。传统的抗抑郁药疗效慢，反应率低。许多研究表明，低剂量的氯胺酮可以产生快速有效的抗抑郁作用。但是，其作用机理有待进一步探索。脂多糖（LPS）用于建立大鼠抑郁模型，PC12神经细胞用于体外实验。α2烟碱乙酰胆碱受体（α7nAChRs）的特定激动剂（2,4）-二甲氧基亚苄基天麻碱二盐酸盐（GTS-21）用于比较氯胺酮的快速抗抑郁作用。使用不同剂量的α7nAChR拮抗剂甲基卡卡他汀（MLA）和α7nAChR-siRNA分别干扰氯胺酮对大鼠和PC12细胞神经炎症的保护作用。MLA干预下调了氯胺酮的抗炎作用，并降低了氯胺酮对神经细胞行为，突触可塑性和Nissl体的影响。此外，MLA的剂量与对大鼠海马的抑制作用呈正相关，而GTS-21的保护作用与氯胺酮一致。这些结果表明，小剂量的氯胺酮可以通过激活抑郁症中的α7nAChR介导的胆碱能抗炎途径（CAP）来产生神经保护作用，从而产生快速的抗抑郁作用。MLA的剂量与对大鼠海马的抑制作用呈正相关，而GTS-21的保护作用与氯胺酮一致。这些结果表明，小剂量的氯胺酮可以通过激活抑郁症中的α7nAChR介导的胆碱能抗炎途径（CAP）来产生神经保护作用，从而产生快速的抗抑郁作用。MLA的剂量与对大鼠海马的抑制作用呈正相关，而GTS-21的保护作用与氯胺酮一致。这些结果表明，小剂量的氯胺酮可以通过激活抑郁症中的α7nAChR介导的胆碱能抗炎途径（CAP）来产生神经保护作用，从而产生快速的抗抑郁作用。