Ascorbic acid supplementation in adolescent rats ameliorates anxiety-like and depressive-like manifestations of nicotine-ethanol abstinence: Role of oxidative stress, inflammatory, and serotonergic mechanisms

IF 1.7 4区医学 Q3 DEVELOPMENTAL BIOLOGY International Journal of Developmental Neuroscience Pub Date : 2024-12-04 DOI:10.1002/jdn.10392

Alireza Najafzadeh, Mobina Mahdizadeh, Samaneh Kakhki, Ali Rahimi, S. Mohammad Ahmadi-Soleimani, Farimah Beheshti

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Abstract

Background

The present study aims to assess the therapeutic potential of vitamin C (Vit C) on anxiety- and depressive-like behavior induced by abstinence from chronic nicotine-ethanol co-exposure in adolescent male rats.

Materials and methods

Adolescent male rats were divided into seven experimental groups with ten rats as follows: 1) vehicle, 2) Nicotine (Nic)-Ethanol (Eth): received Nic (2 mg/kg) and Eth (20%) in drinking water from 21 to 42 days of age, 3–5) Nic-Eth-Vit C 100/200/400: received Nic and Eth from 21 to 42 days of age and received Vit C 100/200/400 mg/kg from 43 to 63 days of age, 6) Nic-Eth-Bupropion (Bup)- Naloxone (Nal): received Nic and Eth from 21 to 42 days of age and received Bup and Nal from 43 to 63 days of age, and 7) Vit C 400 mg/kg: received Vit C 400 mg/kg from 43 to 63 days of age. Behavioral assessments were done by elevated plus maze (EPM), forced swimming test (FST), marble burring test (MBT), and open field tests (OFT). Furthermore, specific biochemical variables associated with oxidative, inflammatory, and serotonergic profiles were quantified.

Results

According to the obtained results, Nic and Eth induced anxiety and depression in treated rats. We showed that two higher doses of Vit C increases the active struggling time in FST and decreases both the time spent in the peripheral zone of OFT and the time spent in the closed arms of EPM. In addition, animals treated by Vit C buried less number of marbles in MBT compared to their control counterparts. Nic and Eth induced oxidative stress and inflammation in cortical tissues of treated rats. Biochemical parameters were improved in the Nic-Eth group receiving Vit C 200/400 mg/kg and Bup-Nal through establishing a balance between oxidant/anti-oxidant and inflammatory/anti-inflammatory mediators. In addition, serotonin level was increased, while Monoamine oxidase (MAO) activity was notably decreased.

Conclusion

The present findings support the beneficial effect of Vit C on anxiety- and depressive-like behavior induced by Nic-Eth withdrawal through various mechanisms such as the promotion of antioxidant defense, suppression of inflammatory mediators, and enhancement of serotoninergic function.

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在青春期大鼠中补充抗坏血酸可改善尼古丁-乙醇戒断的焦虑样和抑郁样表现：氧化应激、炎症和血清素能机制的作用

背景：本研究旨在评估维生素C （Vit C）对青春期雄性大鼠慢性尼古丁-乙醇共暴露戒断引起的焦虑和抑郁样行为的治疗潜力。材料与方法：将青春期雄性大鼠分为7个实验组，每组10只：1)载药，2)尼古丁（Nic)-乙醇（Eth）： 21 ~ 42日龄在饮用水中给予Nic （2 mg/kg）和Eth (20%), 3 ~ 5） Nic-Eth-Vit C 100/200/400: 21 ~ 42日龄给予Nic和Eth， 43 ~ 63日龄给予Vit C 100/200/400 mg/kg， 6) Nic-Eth-安非他酮(Bup)-纳洛酮（Nal）。21 ~ 42日龄给予Nic和Eth， 43 ~ 63日龄给予Bup和Nal； 7)维生素C 400 mg/kg: 43 ~ 63日龄给予维生素C 400 mg/kg。行为学评估采用高架迷宫（EPM）、强迫游泳测试（FST）、大理石毛刺测试（MBT）和野外测试（OFT）。此外，与氧化、炎症和血清素能谱相关的特定生化变量被量化。结果：根据所得结果，Nic和Eth可引起大鼠焦虑和抑郁。我们发现，两个较高剂量的Vit C增加了FST的活跃挣扎时间，减少了OFT外围区和EPM闭合臂的时间。此外，与对照组相比，Vit C处理过的动物在MBT中埋下的弹珠数量更少。Nic和Eth诱导大鼠皮质组织氧化应激和炎症反应。通过在氧化/抗氧化和炎症/抗炎介质之间建立平衡，维生素C 200/400 mg/kg和Bup-Nal给予Nic-Eth组的生化指标得到改善。血清素水平升高，单胺氧化酶（MAO）活性显著降低。结论：本研究结果支持维生素C对Nic-Eth戒断所致的焦虑和抑郁样行为的有益作用，其机制包括促进抗氧化防御、抑制炎症介质和增强血清素能功能。

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来源期刊

International Journal of Developmental Neuroscience 医学-发育生物学

CiteScore

3.30

自引率

5.60%

发文量

审稿时长

6-12 weeks

期刊介绍： International Journal of Developmental Neuroscience publishes original research articles and critical review papers on all fundamental and clinical aspects of nervous system development, renewal and regeneration, as well as on the effects of genetic and environmental perturbations of brain development and homeostasis leading to neurodevelopmental disorders and neurological conditions. Studies describing the involvement of stem cells in nervous system maintenance and disease (including brain tumours), stem cell-based approaches for the investigation of neurodegenerative diseases, roles of neuroinflammation in development and disease, and neuroevolution are also encouraged. Investigations using molecular, cellular, physiological, genetic and epigenetic approaches in model systems ranging from simple invertebrates to human iPSC-based 2D and 3D models are encouraged, as are studies using experimental models that provide behavioural or evolutionary insights. The journal also publishes Special Issues dealing with topics at the cutting edge of research edited by Guest Editors appointed by the Editor in Chief. A major aim of the journal is to facilitate the transfer of fundamental studies of nervous system development, maintenance, and disease to clinical applications. The journal thus intends to disseminate valuable information for both biologists and physicians. International Journal of Developmental Neuroscience is owned and supported by The International Society for Developmental Neuroscience (ISDN), an organization of scientists interested in advancing developmental neuroscience research in the broadest sense.