Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
Research Headquarters, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Int J Neuropsychopharmacol. 2018 Oct 1;21(10):932-937. doi: 10.1093/ijnp/pyy053.
Although previous reports suggest sex-specific differences in the antidepressant actions of (R,S)-ketamine, these differences in the antidepressant actions of (R)-ketamine, which is more potent than (S)-ketamine, are unknown.
Saline or (R)-ketamine was administered 23 hours post lipopolysaccharide administration to adult male or female mice. Subsequently, antidepressant effects were assessed using a forced swimming test. Furthermore, the concentration of (R)-ketamine and its 2 major metabolites, (R)-norketamine and (2R,6R)-hydroxynorketamine, was measured in the plasma and brain after the administration of (R)-ketamine in the mice.
(R)-ketamine (10 mg/kg) significantly attenuated the increased immobility time of forced swimming test in the lipopolysaccharide-treated mice. There were no sex-specific differences in the concentrations of (R)-ketamine and its 2 metabolites in the plasma and brain.
These findings showed no sex-specific differences in terms of the acute antidepressant effects and pharmacokinetic profile of (R)-ketamine.
虽然之前的报告表明（R，S）-氯胺酮的抗抑郁作用存在性别特异性差异，但（R）-氯胺酮的抗抑郁作用是否存在性别差异，而（R）-氯胺酮比（S）-氯胺酮的作用更强，目前尚不清楚。
脂多糖给药后 23 小时，给成年雄性或雌性小鼠注射生理盐水或（R）-氯胺酮。随后，通过强迫游泳试验评估抗抑郁作用。此外，在给予（R）-氯胺酮后，在小鼠的血浆和大脑中测量（R）-氯胺酮及其 2 种主要代谢物（R）-去甲氯胺酮和（2R，6R）-羟基去甲氯胺酮的浓度。
（R）-氯胺酮（10mg/kg）显著减轻了脂多糖处理小鼠强迫游泳试验中不动时间的增加。（R）-氯胺酮及其 2 种代谢物在血浆和大脑中的浓度在性别之间没有差异。
这些发现表明（R）-氯胺酮的急性抗抑郁作用和药代动力学特征在性别方面没有差异。
