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.

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.