Experimenters' sex modulates mouse behaviors and neural responses to ketamine via corticotropin releasing factor.
Experimenters' sex modulates mouse behaviors and neural responses to ketamine via corticotropin releasing factor.
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DOI：
10.1038/s41593-022-01146-x
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发表时间：
2022-09
影响因子：
25
通讯作者：
Gould, Todd D.
中科院分区：
文献类型：
--
作者：
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., Jr.;Duman, Ronald S.;Thompson, Scott M.;Gould, Todd D.
我们发现，人类实验者的性别影响小鼠的行为和反应后，管理的速效抗抑郁药氯胺酮及其生物活性代谢产物（2 R，6 R）-羟基去甲氯胺酮。老鼠表现出厌恶男性实验者的气味，偏好女性实验者的气味，并增加压力敏感性时，由男性实验者处理。这种人类男性气味引起的厌恶和应激易感性是由内嗅皮层中投射到海马CA 1区的促肾上腺皮质激素释放因子（CRF）神经元的激活介导的。在氯胺酮给药前暴露于男性实验者的气味中激活了CA 1投射内嗅皮层CRF神经元，并且该CRF通路的激活调制了氯胺酮的体内和体外抗抑郁样作用。更好地了解人类实验者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重复性，并揭示生物学和药理学机制。
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.
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外侧内嗅皮层损伤损害雄性大鼠的气味背景联想记忆。
影响因子：
4.2
作者：
Persson, Bjorn M.;Ambrozova, Veronika;Duncan, Stephen;Wood, Emma R.;O'Connor, Akira R.;Ainge, James A.
通讯作者：
Ainge, James A.
影响因子：
4.3
作者：
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通讯作者：
Majchrzak M
影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
DOI：
10.1126/science.1190287
发表时间：
2010-08-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li N;Lee B;Liu RJ;Banasr M;Dwyer JM;Iwata M;Li XY;Aghajanian G;Duman RS
通讯作者：
Duman RS
DOI：
10.1073/pnas.1816071116
发表时间：
2019-03-12
影响因子：
11.1
作者：
Lumsden, Eric W.;Troppoli, Timothy A.;Gould, Todd D.
通讯作者：
Gould, Todd D.