Najafzadeh Alireza, Mahdizadeh Mobina, Kakhki Samaneh, Rahimi Ali, Ahmadi-Soleimani S Mohammad, Beheshti Farimah
Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran.
Student Research Committee, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran.
Int J Dev Neurosci. 2025 Feb;85(1):e10392. doi: 10.1002/jdn.10392. Epub 2024 Dec 4.
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.
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.
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.
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.
本研究旨在评估维生素C（Vit C）对青春期雄性大鼠因戒除慢性尼古丁 - 乙醇共同暴露所诱导的焦虑样和抑郁样行为的治疗潜力。
将青春期雄性大鼠分为七个实验组，每组十只大鼠，分组如下：1）溶剂对照组；2）尼古丁（Nic）-乙醇（Eth）组：在21至42日龄期间饮用含Nic（2mg/kg）和Eth（20%）的水；3 - 5）Nic - Eth - Vit C 100/200/400组：在21至42日龄期间接受Nic和Eth，在43至63日龄期间接受100/200/400mg/kg的Vit C；6）Nic - Eth - 安非他酮（Bup）-纳洛酮（Nal）组：在21至42日龄期间接受Nic和Eth，在43至63日龄期间接受Bup和Nal；7）Vit C 400mg/kg组：在43至63日龄期间接受400mg/kg的Vit C。通过高架十字迷宫（EPM）、强迫游泳试验（FST）、大理石埋藏试验（MBT）和旷场试验（OFT）进行行为评估。此外，对与氧化、炎症和血清素能谱相关的特定生化变量进行了定量分析。
根据所得结果，Nic和Eth在受试大鼠中诱导了焦虑和抑郁。我们发现，两种较高剂量的Vit C增加了FST中的主动挣扎时间，并减少了OFT外周区域的停留时间以及EPM封闭臂中的停留时间。此外，与对照动物相比，接受Vit C治疗的动物在MBT中埋藏的大理石数量更少。Nic和Eth在受试大鼠的皮质组织中诱导了氧化应激和炎症。通过在氧化剂/抗氧化剂和炎症/抗炎介质之间建立平衡，接受200/4mg/kg Vit C和Bup - Nal的Nic - Eth组的生化参数得到改善。此外，血清素水平升高，而单胺氧化酶（MAO）活性显著降低。
本研究结果支持Vit C通过多种机制，如促进抗氧化防御、抑制炎症介质和增强血清素能功能，对Nic - Eth戒断所诱导的焦虑样和抑郁样行为具有有益作用。
