Ronan Depoortère, Mariusz Papp, Piotr Gruca, Ewa Litwa, Magdalena Lason, Dominika Biała, Adrian Newman-Tancredi
{"title":"氯胺酮在大鼠慢性轻度应激模型中的抗抑郁样活性需要激活皮质5-HT1A受体。","authors":"Ronan Depoortère, Mariusz Papp, Piotr Gruca, Ewa Litwa, Magdalena Lason, Dominika Biała, Adrian Newman-Tancredi","doi":"10.1097/FBP.0000000000000809","DOIUrl":null,"url":null,"abstract":"<p><p>Ketamine displays efficacious rapid-acting antidepressant (RAAD) activity in the rat chronic mild stress (CMS) model. It rapidly reverses anhedonia (CMS-induced sucrose consumption deficit) and attenuates working memory deficit (novel object recognition: NOR) following both systemic (intraperitoneal, i.p.) administration or local administration in the prefrontal cortex (PFC). However, the receptor mechanisms underlying these effects remain to be clarified and may involve activation of serotonin 5-HT 1A receptors, as previously found in experiments using the forced swim test. The present study explored the contribution of PFC 5-HT 1A receptors in ketamine's RAAD activity in the CMS model. Ketamine (10 mg/kg i.p.) reversed CMS-induced sucrose consumption and working memory (NOR test) deficits. Notably, unilateral PFC microinjections of a 5-HT 1A receptor antagonist, WAY-100635 (2 µg), prevented the antidepressant-like and pro-cognitive activity of systemic ketamine on sucrose consumption and working memory deficits. These data indicate that the RAAD activity of ketamine in the rat CMS model requires activation of PFC 5-HT 1A receptors. They also reinforce the notion that drugs that directly activate PFC 5-HT 1A receptors could constitute an alternative to ketamine as a promising strategy to achieve RAAD effects, with additional benefits against cognitive deficits in depressed patients, but without ketamine's troublesome side-effects and requirements for in-patient supervision.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"182-188"},"PeriodicalIF":1.6000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The antidepressant-like activity of ketamine in the rat chronic mild stress model requires activation of cortical 5-HT 1A receptors.\",\"authors\":\"Ronan Depoortère, Mariusz Papp, Piotr Gruca, Ewa Litwa, Magdalena Lason, Dominika Biała, Adrian Newman-Tancredi\",\"doi\":\"10.1097/FBP.0000000000000809\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Ketamine displays efficacious rapid-acting antidepressant (RAAD) activity in the rat chronic mild stress (CMS) model. It rapidly reverses anhedonia (CMS-induced sucrose consumption deficit) and attenuates working memory deficit (novel object recognition: NOR) following both systemic (intraperitoneal, i.p.) administration or local administration in the prefrontal cortex (PFC). However, the receptor mechanisms underlying these effects remain to be clarified and may involve activation of serotonin 5-HT 1A receptors, as previously found in experiments using the forced swim test. The present study explored the contribution of PFC 5-HT 1A receptors in ketamine's RAAD activity in the CMS model. Ketamine (10 mg/kg i.p.) reversed CMS-induced sucrose consumption and working memory (NOR test) deficits. Notably, unilateral PFC microinjections of a 5-HT 1A receptor antagonist, WAY-100635 (2 µg), prevented the antidepressant-like and pro-cognitive activity of systemic ketamine on sucrose consumption and working memory deficits. These data indicate that the RAAD activity of ketamine in the rat CMS model requires activation of PFC 5-HT 1A receptors. They also reinforce the notion that drugs that directly activate PFC 5-HT 1A receptors could constitute an alternative to ketamine as a promising strategy to achieve RAAD effects, with additional benefits against cognitive deficits in depressed patients, but without ketamine's troublesome side-effects and requirements for in-patient supervision.</p>\",\"PeriodicalId\":8832,\"journal\":{\"name\":\"Behavioural Pharmacology\",\"volume\":\" \",\"pages\":\"182-188\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2025-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Behavioural Pharmacology\",\"FirstCategoryId\":\"102\",\"ListUrlMain\":\"https://doi.org/10.1097/FBP.0000000000000809\",\"RegionNum\":4,\"RegionCategory\":\"心理学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BEHAVIORAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Behavioural Pharmacology","FirstCategoryId":"102","ListUrlMain":"https://doi.org/10.1097/FBP.0000000000000809","RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/16 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
The antidepressant-like activity of ketamine in the rat chronic mild stress model requires activation of cortical 5-HT 1A receptors.
Ketamine displays efficacious rapid-acting antidepressant (RAAD) activity in the rat chronic mild stress (CMS) model. It rapidly reverses anhedonia (CMS-induced sucrose consumption deficit) and attenuates working memory deficit (novel object recognition: NOR) following both systemic (intraperitoneal, i.p.) administration or local administration in the prefrontal cortex (PFC). However, the receptor mechanisms underlying these effects remain to be clarified and may involve activation of serotonin 5-HT 1A receptors, as previously found in experiments using the forced swim test. The present study explored the contribution of PFC 5-HT 1A receptors in ketamine's RAAD activity in the CMS model. Ketamine (10 mg/kg i.p.) reversed CMS-induced sucrose consumption and working memory (NOR test) deficits. Notably, unilateral PFC microinjections of a 5-HT 1A receptor antagonist, WAY-100635 (2 µg), prevented the antidepressant-like and pro-cognitive activity of systemic ketamine on sucrose consumption and working memory deficits. These data indicate that the RAAD activity of ketamine in the rat CMS model requires activation of PFC 5-HT 1A receptors. They also reinforce the notion that drugs that directly activate PFC 5-HT 1A receptors could constitute an alternative to ketamine as a promising strategy to achieve RAAD effects, with additional benefits against cognitive deficits in depressed patients, but without ketamine's troublesome side-effects and requirements for in-patient supervision.
期刊介绍:
Behavioural Pharmacology accepts original full and short research reports in diverse areas ranging from ethopharmacology to the pharmacology of schedule-controlled operant behaviour, provided that their primary focus is behavioural. Suitable topics include drug, chemical and hormonal effects on behaviour, the neurochemical mechanisms under-lying behaviour, and behavioural methods for the study of drug action. Both animal and human studies are welcome; however, studies reporting neurochemical data should have a predominantly behavioural focus, and human studies should not consist exclusively of clinical trials or case reports. Preference is given to studies that demonstrate and develop the potential of behavioural methods, and to papers reporting findings of direct relevance to clinical problems. Papers making a significant theoretical contribution are particularly welcome and, where possible and merited, space is made available for authors to explore fully the theoretical implications of their findings. Reviews of an area of the literature or at an appropriate stage in the development of an author’s own work are welcome. Commentaries in areas of current interest are also considered for publication, as are Reviews and Commentaries in areas outside behavioural pharmacology, but of importance and interest to behavioural pharmacologists. Behavioural Pharmacology publishes frequent Special Issues on current hot topics. The editors welcome correspondence about whether a paper in preparation might be suitable for inclusion in a Special Issue.