Henry Wellcome Laboratories for Integrative Neuroendocrinology, School of Medicine, University of Bristol, Bristol, UK.
School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, UK.
J Neuroendocrinol. 2022 Oct;34(10):e13194. doi: 10.1111/jne.13194. Epub 2022 Sep 2.
Over 50% of depressed patients show hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Conventional therapy takes weeks to months to improve symptoms. Ketamine has rapid onset antidepressant effects. Yet its action on HPA axis activity is poorly understood. Here, we measured the corticosterone (CORT) response to ketamine administered at different times of day in the Wistar-Kyoto (WKY) rat. In male rats, blood was collected every 10 min for 28 h using an automated blood sampling system. Ketamine (5/10/25 mg · kg) was infused through a subcutaneous cannula at two time points-during the active and inactive period. CORT levels in blood were measured in response to ketamine using a radioimmunoassay. WKY rats displayed robust circadian secretion of corticosterone and was not overly different to Sprague Dawley rats. Ketamine (all doses) significantly increased CORT response at both infusion times. However, a dose dependent effect and marked increase over baseline was observed when ketamine was administered during the inactive phase. Ketamine has a robust and rapid effect on HPA axis function. The timing of ketamine injection may prove crucial for glucocorticoid-mediated action in depression.
超过 50%的抑郁症患者表现出下丘脑-垂体-肾上腺 (HPA) 轴的过度活跃。常规治疗需要数周甚至数月才能改善症状。氯胺酮具有快速抗抑郁作用。然而，其对 HPA 轴活动的作用知之甚少。在这里，我们测量了在 Wistar-Kyoto (WKY) 大鼠中，在一天的不同时间给予氯胺酮时，皮质酮 (CORT) 的反应。在雄性大鼠中，使用自动采血系统每 10 分钟采集一次血样，持续 28 小时。氯胺酮 (5/10/25mg·kg) 通过皮下套管在活动期和不活动期两个时间点输注。使用放射免疫法测量血液中皮质酮对氯胺酮的反应。WKY 大鼠表现出皮质酮的强大昼夜分泌，与 Sprague Dawley 大鼠没有太大区别。氯胺酮（所有剂量）在两个输注时间都显著增加了 CORT 反应。然而，当氯胺酮在不活动期给药时，观察到剂量依赖性效应和明显高于基线的增加。氯胺酮对 HPA 轴功能有强大而快速的作用。氯胺酮注射的时间可能对糖皮质激素介导的抑郁症治疗至关重要。
