小柯机器人

美国马里兰大学Todd D. Gould团队近期取得重要工作进展，他们研究发现实验者的性别通过促肾上腺皮质激素释放因子调节小鼠行为和对氯胺酮的神经反应。相关论文于2022年8月30日在线发表于《自然—神经科学》杂志上。

研究人员表明，人类实验者的性别会影响小鼠在服用速效抗抑郁药氯胺酮及其生物活性代谢物（2R,6R）-羟基去甲氯胺酮后的行为和反应。小鼠表现出厌恶男性实验者的气味，偏爱女性实验者的气味，并且在男性实验者处理时对压力的敏感性增加。这种人类-男性-气味引起的厌恶和压力敏感性，是由投射到海马区CA1的内嗅皮层中促肾上腺皮质激素释放因子（CRF）神经元的激活所介导的。

在给予氯胺酮之前暴露于男性实验者的气味，会激活CA1投射的内嗅皮层CRF神经元，并且该CRF通路的激活会调节氯胺酮的体内和体外抗抑郁作用。更好地了解人类实验者的性别对啮齿动物研究结果的具体和定量贡献，可能会提高研究之间的可复制性，准确地揭示生物学和药理学相关的机制。

附：英文原文

Title: Experimenters’ sex modulates mouse behaviors and neural responses to ketamine via corticotropin releasing factor

Author: Georgiou, Polymnia, Zanos, Panos, Mou, Ta-Chung M., An, Xiaoxian, Gerhard, Danielle M., Dryanovski, Dilyan I., Potter, Liam E., Highland, Jaclyn N., Jenne, Carleigh E., Stewart, Brent W., Pultorak, Katherine J., Yuan, Peixiong, Powels, Chris F., Lovett, Jacqueline, Pereira, Edna F. R., Clark, Sarah M., Tonelli, Leonardo H., Moaddel, Ruin, Zarate, Carlos A., Duman, Ronald S., Thompson, Scott M., Gould, Todd D.

Issue&Volume: 2022-08-30

Abstract: We show that the sex of human experimenters affects mouse behaviors and responses following administration of the rapid-acting antidepressant ketamine and its bioactive metabolite (2R,6R)-hydroxynorketamine. Mice showed aversion to the scent of male experimenters, preference for the scent of female experimenters and increased stress susceptibility when handled by male experimenters. This human-male-scent-induced aversion and stress susceptibility was mediated by the activation of corticotropin-releasing factor (CRF) neurons in the entorhinal cortex that project to hippocampal area CA1. Exposure to the scent of male experimenters before ketamine administration activated CA1-projecting entorhinal cortex CRF neurons, and activation of this CRF pathway modulated in vivo and in vitro antidepressant-like effects of ketamine. A better understanding of the specific and quantitative contributions of the sex of human experimenters to study outcomes in rodents may improve replicability between studies and, as we have shown, reveal biological and pharmacological mechanisms.

DOI: 10.1038/s41593-022-01146-x

Source: https://www.nature.com/articles/s41593-022-01146-x

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex