Corticosterone as a Potential Confounding Factor in Delineating Mechanisms Underlying Ketamine's Rapid Antidepressant Actions.
Corticosterone as a Potential Confounding Factor in Delineating Mechanisms Underlying Ketamine's Rapid Antidepressant Actions.
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DOI：
10.3389/fphar.2020.590221
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发表时间：
2020
影响因子：
5.6
通讯作者：
Yuan LL
中科院分区：
文献类型：
--
作者：
Wegman-Points L;Pope B;Zobel-Mask A;Winter L;Wauson E;Duric V;Yuan LL
最近对亚麻醉剂量氯胺酮的快速抗抑郁作用的研究已经确定了一系列在给药后数小时内激活的相关蛋白级联反应。在这些激活级联反应之前或同时，氯胺酮治疗产生解离性和拟精神病性副作用，沿着循环糖皮质激素的增加。在大鼠中，我们观察到低剂量氯胺酮（10 mg/kg）给药后1小时内血清和脑组织中皮质酮水平均增加3倍以上，但（2 R，6 R）-羟基去甲氯胺酮（HNK）（10 mg/kg）给药后未增加，这是一种氯胺酮代谢物，在啮齿动物中可产生抗抑郁药样作用，而不会诱导即刻副作用。氯胺酮注射动物的海马组织（而非HNK）显示糖皮质激素受体信号传导的下游效应物sgk 1表达显著增加。为了研究氯胺酮副作用的意识感觉在皮质酮释放中的作用，我们评估了异氟烷麻醉下氯胺酮给药后的血清皮质酮水平。在麻醉下，氯胺酮未能增加循环皮质酮水平相对于盐水对照。与其抗抑郁作用同时，氯胺酮产生糖皮质激素的释放，可能与干扰性认知副作用和不同分子途径的激活有关，当试图描述其抗抑郁功能的分子机制时，应考虑到这一点。
Recent research into the rapid antidepressant effect of subanesthetic doses of ketamine have identified a series of relevant protein cascades activated within hours of administration. Prior to, or concurrent with, these activation cascades, ketamine treatment generates dissociative and psychotomimetic side effects along with an increase in circulating glucocorticoids. In rats, we observed an over 3-fold increase in corticosterone levels in both serum and brain tissue, within an hour of administration of low dose ketamine (10 mg/kg), but not with (2R, 6R)-hydroxynorketamine (HNK) (10 mg/kg), a ketamine metabolite shown to produce antidepressant-like action in rodents without inducing immediate side-effects. Hippocampal tissue from ketamine, but not HNK, injected animals displayed a significant increase in the expression of sgk1, a downstream effector of glucocorticoid receptor signaling. To examine the role conscious sensation of ketamine’s side effects plays in the release of corticosterone, we assessed serum corticosterone levels after ketamine administration while under isoflurane anesthesia. Under anesthesia, ketamine failed to increase circulating corticosterone levels relative to saline controls. Concurrent with its antidepressant effects, ketamine generates a release of glucocorticoids potentially linked to disturbing cognitive side effects and the activation of distinct molecular pathways which should be considered when attempting to delineate the molecular mechanisms of its antidepressant function.
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影响因子：
--
作者：
Gourley, Shannon L;Taylor, Jane R
通讯作者：
Taylor, Jane R
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.
影响因子：
2.7
作者：
Bekhbat M;Merrill L;Kelly SD;Lee VK;Neigh GN
通讯作者：
Neigh GN
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
影响因子：
5.2
作者：
Gourley SL;Wu FJ;Taylor JR
通讯作者：
Taylor JR