Oleoylethanolamide restores stress-induced prepulse inhibition deficits and modulates inflammatory signaling in a sex-dependent manner.

IF 3.5 3区 医学 Q2 NEUROSCIENCES
Psychopharmacology Pub Date : 2025-05-01 Epub Date: 2023-06-14 DOI:10.1007/s00213-023-06403-w
Macarena González-Portilla, Sandra Montagud-Romero, Fernando Rodríguez de Fonseca, Marta Rodríguez-Arias
{"title":"Oleoylethanolamide restores stress-induced prepulse inhibition deficits and modulates inflammatory signaling in a sex-dependent manner.","authors":"Macarena González-Portilla, Sandra Montagud-Romero, Fernando Rodríguez de Fonseca, Marta Rodríguez-Arias","doi":"10.1007/s00213-023-06403-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale: </strong>Social stress contributes to the development of depressive and anxiety symptomatology and promotes pro-inflammatory signaling in the central nervous system. In this study, we explored the effects of a lipid messenger with anti-inflammatory properties - oleoylethanolamide (OEA) - on the behavioral deficits caused by social stress in both male and female mice.</p><p><strong>Methods: </strong>Adult mice were assigned to an experimental group according to the stress condition (control or stress) and treatment (vehicle or OEA, 10 mg/kg, i.p.). Male mice in the stress condition underwent a protocol consisting of four social defeat (SD) encounters. In the case of female mice, we employed a procedure of vicarious SD. After the stress protocol resumed, anxiety, depressive-like behavior, social interaction, and prepulse inhibition (PPI) were assessed. In addition, we characterized the stress-induced inflammatory profile by measuring IL-6 and CX3CL1 levels in the striatum and hippocampus.</p><p><strong>Results: </strong>Our results showed that both SD and VSD induced behavioral alterations. We found that OEA treatment restored PPI deficits in socially defeated mice. Also, OEA affected differently stress-induced anxiety and depressive-like behavior in male and female mice. Biochemical analyses showed that both male and female stressed mice showed increased levels of IL-6 in the striatum compared to control mice. Similarly, VSD female mice exhibited increased striatal CX3CL1 levels. These neuroinflammation-associated signals were not affected by OEA treatment.</p><p><strong>Conclusions: </strong>In summary, our results confirm that SD and VSD induced behavioral deficits together with inflammatory signaling in the striatum and hippocampus. We observed that OEA treatment reverses stress-induced PPI alterations in male and female mice. These data suggest that OEA can exert a buffering effect on stress-related sensorimotor gating behavioral processing.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"913-928"},"PeriodicalIF":3.5000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043760/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00213-023-06403-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/6/14 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0

Abstract

Rationale: Social stress contributes to the development of depressive and anxiety symptomatology and promotes pro-inflammatory signaling in the central nervous system. In this study, we explored the effects of a lipid messenger with anti-inflammatory properties - oleoylethanolamide (OEA) - on the behavioral deficits caused by social stress in both male and female mice.

Methods: Adult mice were assigned to an experimental group according to the stress condition (control or stress) and treatment (vehicle or OEA, 10 mg/kg, i.p.). Male mice in the stress condition underwent a protocol consisting of four social defeat (SD) encounters. In the case of female mice, we employed a procedure of vicarious SD. After the stress protocol resumed, anxiety, depressive-like behavior, social interaction, and prepulse inhibition (PPI) were assessed. In addition, we characterized the stress-induced inflammatory profile by measuring IL-6 and CX3CL1 levels in the striatum and hippocampus.

Results: Our results showed that both SD and VSD induced behavioral alterations. We found that OEA treatment restored PPI deficits in socially defeated mice. Also, OEA affected differently stress-induced anxiety and depressive-like behavior in male and female mice. Biochemical analyses showed that both male and female stressed mice showed increased levels of IL-6 in the striatum compared to control mice. Similarly, VSD female mice exhibited increased striatal CX3CL1 levels. These neuroinflammation-associated signals were not affected by OEA treatment.

Conclusions: In summary, our results confirm that SD and VSD induced behavioral deficits together with inflammatory signaling in the striatum and hippocampus. We observed that OEA treatment reverses stress-induced PPI alterations in male and female mice. These data suggest that OEA can exert a buffering effect on stress-related sensorimotor gating behavioral processing.

油基乙醇酰胺恢复应激诱导的脉冲前抑制缺陷,并以性别依赖的方式调节炎症信号。
理由:社会压力有助于抑郁和焦虑症状的发展,并促进中枢神经系统的促炎信号。在这项研究中,我们探讨了具有抗炎特性的脂质信使-油基乙醇酰胺(OEA)对雄性和雌性小鼠由社会压力引起的行为缺陷的影响。方法:将成年小鼠按应激状态(对照组或应激组)和治疗(对照或OEA, 10 mg/kg, i.p)分为实验组。应激条件下的雄性小鼠接受了由四次社会失败(SD)遭遇组成的方案。在雌性小鼠的情况下,我们采用了替代SD程序。应激方案恢复后,评估焦虑、抑郁样行为、社会互动和脉搏前抑制(PPI)。此外,我们通过测量纹状体和海马中的IL-6和CX3CL1水平来表征应激诱导的炎症谱。结果:我们的研究结果表明,SD和VSD都能引起行为改变。我们发现OEA治疗恢复了社交失败小鼠的PPI缺陷。此外,OEA对雄性和雌性小鼠应激诱导的焦虑和抑郁样行为的影响不同。生化分析表明,与对照组小鼠相比,雄性和雌性应激小鼠纹状体中的IL-6水平均有所增加。同样,VSD雌性小鼠纹状体CX3CL1水平升高。这些神经炎症相关信号不受OEA治疗的影响。结论:总之,我们的研究结果证实了SD和VSD在纹状体和海马中引起行为缺陷以及炎症信号。我们观察到OEA治疗逆转应激诱导的雄性和雌性小鼠PPI改变。这些数据表明,OEA对应激相关的感觉运动门控行为加工具有缓冲作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Psychopharmacology
Psychopharmacology 医学-精神病学
CiteScore
7.10
自引率
5.90%
发文量
257
审稿时长
2-4 weeks
期刊介绍: Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信