Sex-dependent role of Neuropeptide-S on anxiety, fear conditioning, and alcohol seeking in alcohol preferring rats

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology Pub Date : 2025-07-23 DOI:10.1016/j.neuropharm.2025.110598

Min Li , Sara De Carlo , Laura Soverchia , Scott P. Runyon , Stewart Clark , Marisa Roberto , Carolina L. Haass-Koffler , Roberto Ciccocioppo , Douglas J. Sheffler , Nazzareno Cannella

{"title":"Sex-dependent role of Neuropeptide-S on anxiety, fear conditioning, and alcohol seeking in alcohol preferring rats","authors":"Min Li , Sara De Carlo , Laura Soverchia , Scott P. Runyon , Stewart Clark , Marisa Roberto , Carolina L. Haass-Koffler , Roberto Ciccocioppo , Douglas J. Sheffler , Nazzareno Cannella","doi":"10.1016/j.neuropharm.2025.110598","DOIUrl":null,"url":null,"abstract":"<div><div>Alcohol Use Disorder (AUD) is a global health concern, with stress playing a crucial role in its development and persistence. Currently, no pharmacotherapies specifically targeting stress are approved for AUD treatment. Neuropeptide S (NPS) plays a dual role in stress regulation, exhibiting both anxiolytic and stress-enhancing effects. While NPS reduces alcohol self-administration (ASA) in alcohol preferring rats, its role in AUD-related stress and anxiety remains unclear.</div><div>This study investigated the behavioral effects of NPS in male and female Marchigian Sardinian alcohol-preferring (msP) rats. To assess its impact on locomotion, anxiety, and fear memory, we conducted an open-field, an elevated plus maze (EPM), and a fear conditioning (FC) paradigm following intracerebroventricular administration of NPS. Furthermore, we examined the effects of NPS on ASA and yohimbine-induced reinstatement of alcohol-seeking in msP rats.</div><div>Our results indicate that NPS administration increased locomotor activity in both sexes and selectively alleviated generalized anxiety levels in male rats in the EPM test. In the FC task, administration of NPS immediately after FC test facilitated the extinction of fear memories in females but not in males. Notably, NPS reduced ASA in both female and male rats but did not alter yohimbine-induced reinstatement of alcohol-seeking. In conclusion, NPS modulates anxiety in a sex-dependent manner. Since both alcohol and NPS alleviate anxiety and fear conditioning in msP rats, NPS may reduce alcohol intake by replacing the anxiolytic properties of alcohol. These effects appear to be sex-dependent, with NPS primarily alleviating generalized anxiety in males and facilitating fear extinction in females.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110598"},"PeriodicalIF":4.6000,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuropharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0028390825003065","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Alcohol Use Disorder (AUD) is a global health concern, with stress playing a crucial role in its development and persistence. Currently, no pharmacotherapies specifically targeting stress are approved for AUD treatment. Neuropeptide S (NPS) plays a dual role in stress regulation, exhibiting both anxiolytic and stress-enhancing effects. While NPS reduces alcohol self-administration (ASA) in alcohol preferring rats, its role in AUD-related stress and anxiety remains unclear.

This study investigated the behavioral effects of NPS in male and female Marchigian Sardinian alcohol-preferring (msP) rats. To assess its impact on locomotion, anxiety, and fear memory, we conducted an open-field, an elevated plus maze (EPM), and a fear conditioning (FC) paradigm following intracerebroventricular administration of NPS. Furthermore, we examined the effects of NPS on ASA and yohimbine-induced reinstatement of alcohol-seeking in msP rats.

Our results indicate that NPS administration increased locomotor activity in both sexes and selectively alleviated generalized anxiety levels in male rats in the EPM test. In the FC task, administration of NPS immediately after FC test facilitated the extinction of fear memories in females but not in males. Notably, NPS reduced ASA in both female and male rats but did not alter yohimbine-induced reinstatement of alcohol-seeking. In conclusion, NPS modulates anxiety in a sex-dependent manner. Since both alcohol and NPS alleviate anxiety and fear conditioning in msP rats, NPS may reduce alcohol intake by replacing the anxiolytic properties of alcohol. These effects appear to be sex-dependent, with NPS primarily alleviating generalized anxiety in males and facilitating fear extinction in females.

查看原文本刊更多论文

神经肽- s在酒精偏好大鼠焦虑、恐惧条件反射和酒精寻求中的性别依赖作用

酒精使用障碍（AUD）是一个全球性的健康问题，压力在其发展和持续中起着至关重要的作用。目前，没有专门针对压力的药物疗法被批准用于AUD治疗。神经肽S （NPS）在应激调节中具有双重作用，既具有抗焦虑作用，又具有应激增强作用。虽然NPS减少了酒精偏好大鼠的酒精自我给药（ASA），但其在aud相关压力和焦虑中的作用尚不清楚。本研究探讨了NPS对雄性和雌性撒丁岛嗜酒大鼠（msP）的行为影响。为了评估其对运动、焦虑和恐惧记忆的影响，我们在脑室内给药NPS后进行了开放场、升高+迷宫（EPM）和恐惧条件反射（FC）范式。此外，我们还研究了NPS对msP大鼠ASA和育亨宾诱导的酒精寻求恢复的影响。我们的研究结果表明，在EPM测试中，NPS给药增加了两性的运动活动，并选择性地减轻了雄性大鼠的广泛性焦虑水平。在FC任务中，在FC测试后立即给药NPS促进了女性恐惧记忆的消失，但对男性没有促进作用。值得注意的是，NPS降低了雌性和雄性大鼠的ASA，但没有改变育亨宾诱导的寻求酒精的恢复。总之，NPS以性别依赖的方式调节焦虑。由于酒精和NPS都能减轻msP大鼠的焦虑和恐惧条件反射，NPS可能通过取代酒精的抗焦虑特性来减少酒精摄入量。这些效果似乎是性别依赖的，NPS主要缓解男性的广泛性焦虑，促进女性的恐惧消除。

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

Neuropharmacology 医学-神经科学

CiteScore

10.00

自引率

4.30%

发文量

288

审稿时长

45 days

期刊介绍： Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).