Attila Tóth, Katalin Sviatkó, László Détári, Tünde Hajnik
{"title":"Ketamine affects homeostatic sleep regulation in the absence of the circadian sleep-regulating component in freely moving rats","authors":"Attila Tóth, Katalin Sviatkó, László Détári, Tünde Hajnik","doi":"10.1016/j.pbb.2023.173556","DOIUrl":null,"url":null,"abstract":"<div><p>Pharmacological effects of ketamine may affect homeostatic sleep regulation via slow wave related mechanisms.</p><p>In the present study effects of ketamine applied at anesthetic dose (80 mg/kg) were tested on neocortical electric activity for 24 h in freely moving rats. Ketamine effects were compared to changes during control (saline) injections and after 6 h gentle handling sleep deprivation (SD). As circadian factors may mask drug effects, an illumination protocol consisting of short light-dark cycles was applied.</p><p>Ketamine application induced a short hypnotic stage with characteristic slow cortical rhythm followed by a long-lasting hyperactive waking resulting pharmacological SD. Coherence analysis indicated an increased level of local synchronization in broad local field potential frequency ranges during hyperactive waking but not during natural- or SD-evoked waking. Both slow wave sleep and rapid eye movement sleep were replaced after the termination of the ketamine effect.</p><p>Our results show that both ketamine-induced hypnotic state and hyperactive waking can induce homeostatic sleep pressure with comparable intensity as 6 h SD, but ketamine-induced waking was different compared to the SD-evoked one. Both types of waking stages were different compared to spontaneous waking but all three types of wakefulness can engage the homeostatic sleep regulating machinery to generate sleep pressure dissipated by subsequent sleep. Current-source density analysis of the slow waves showed that cortical transmembrane currents were stronger during ketamine-induced hypnotic stage compared to both sleep replacement after SD and ketamine application, but intracortical activation patterns showed only quantitative differences.</p><p>These findings may hold some translational value for human medical ketamine applications aiming the treatment of depression-associated sleep problems, which can be alleviated by the homeostatic sleep effect of the drug without the need for an intact circadian regulation.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"225 ","pages":"Article 173556"},"PeriodicalIF":3.3000,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacology Biochemistry and Behavior","FirstCategoryId":"102","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0091305723000436","RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Pharmacological effects of ketamine may affect homeostatic sleep regulation via slow wave related mechanisms.
In the present study effects of ketamine applied at anesthetic dose (80 mg/kg) were tested on neocortical electric activity for 24 h in freely moving rats. Ketamine effects were compared to changes during control (saline) injections and after 6 h gentle handling sleep deprivation (SD). As circadian factors may mask drug effects, an illumination protocol consisting of short light-dark cycles was applied.
Ketamine application induced a short hypnotic stage with characteristic slow cortical rhythm followed by a long-lasting hyperactive waking resulting pharmacological SD. Coherence analysis indicated an increased level of local synchronization in broad local field potential frequency ranges during hyperactive waking but not during natural- or SD-evoked waking. Both slow wave sleep and rapid eye movement sleep were replaced after the termination of the ketamine effect.
Our results show that both ketamine-induced hypnotic state and hyperactive waking can induce homeostatic sleep pressure with comparable intensity as 6 h SD, but ketamine-induced waking was different compared to the SD-evoked one. Both types of waking stages were different compared to spontaneous waking but all three types of wakefulness can engage the homeostatic sleep regulating machinery to generate sleep pressure dissipated by subsequent sleep. Current-source density analysis of the slow waves showed that cortical transmembrane currents were stronger during ketamine-induced hypnotic stage compared to both sleep replacement after SD and ketamine application, but intracortical activation patterns showed only quantitative differences.
These findings may hold some translational value for human medical ketamine applications aiming the treatment of depression-associated sleep problems, which can be alleviated by the homeostatic sleep effect of the drug without the need for an intact circadian regulation.
氯胺酮的药理作用可能通过慢波相关机制影响稳态睡眠调节。在本研究中，测试了麻醉剂量（80mg/kg）的氯胺酮对自由运动大鼠皮层电活动24小时的影响。将氯胺酮效应与对照（生理盐水）注射期间和6小时温和处理睡眠剥夺（SD）后的变化进行比较。由于昼夜节律因素可能掩盖药物效应，因此采用了由短明暗周期组成的照明方案。氯胺酮应用诱导了一个短暂的催眠阶段，具有特征性的缓慢皮层节律，随后是长期的过度活跃清醒，从而产生药理学SD。一致性分析表明，在过度活跃清醒期间，在广泛的局部场电位频率范围内，局部同步水平增加，但在自然或SD诱发的清醒期间没有。氯胺酮效应终止后，慢波睡眠和快速眼动睡眠均被取代。我们的研究结果表明，氯胺酮诱导的催眠状态和过度活跃清醒都能诱导稳态睡眠压力，其强度与6 h SD相当，但氯胺酮诱导的清醒与SD诱导的清醒不同。与自发清醒相比，这两种类型的清醒阶段都不同，但所有三种类型的觉醒都可以参与稳态睡眠调节机制，产生通过随后的睡眠消散的睡眠压力。慢波的电流源密度分析显示，与SD和氯胺酮应用后的睡眠替代相比，氯胺酮诱导的催眠阶段的皮层跨膜电流更强，但皮层内激活模式仅显示出定量差异。这些发现可能对旨在治疗抑郁症相关睡眠问题的人类医用氯胺酮应用具有一定的转化价值，该药物的稳态睡眠效果可以缓解抑郁相关睡眠问题，而不需要完整的昼夜节律调节。
期刊介绍：
Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
