Vitamin B12 reversed anxiety and depression induced by adolescent nicotine withdrawal through alteration the inflammatory, oxidative and serotoninergic profiles in male rats.

ABSTRACT

BACKGROUND: The present study aims to assess the effect of vitamin B12 (Vit B12) on depression-like behavior caused by nicotine (Nic) withdrawal, which is more likely due to the anxiogenic effect of Nic in adolescent male rats, through assessing behavioral and biochemical analysis. METHODS: Adolescent male rats were divided into vehicle (received normal saline), and experimental groups that received Nic (2 mg/kg, intraperitoneally (i.p.)) for three consecutive weeks and after that, the group that received normal saline was divided into two groups, one of which returned to a regular diet, and the second one received Vit B12 (1.5 mg/kg). The Nic group was divided into five groups, one of which received bupropion (Bup, 20 mg/kg), three of which received different doses of Vit B12 (0.5, 1, and 1.5 mg/kg), and the last one returned to a normal diet without treatment, which was considered as the withdrawal period. RESULTS: Behavioral analysis showed that Nic withdrawal induced anxiety and depression. Vit B12 and Bup reduced anxiety and depression induced by Nic withdrawal. The biochemical analysis demonstrated the more activity of oxidative stress factors and pro-inflammatory cytokines in which Nic was administered, whereas both Vit B12 and Bup reversed the results and improved the activity of both antioxidant and anti-inflammatory parameters. Furthermore, both serum and cortical Vit B12 levels dramatically decreased in nicotine group, whereas treatment with both Vit B12 and Bup as desirable treatments corrected Vit B12 levels. CONCLUSION: According to the present findings, the results revealed that Vit B12 is comparable with Bup in attenuation of Nic withdrawal symptoms. In addition, both Bup and Vit B12 improved the decreased serum and cortical levels of Vit B12, which caused by nicotine. Administration of Vit B12 in normal animals demonstrated better results in reducing antioxidant and anti-inflammatory parameters, which explores new hope to introduce Vit B12 as a novel antioxidant and anti-inflammatory agent to treat not only withdrawal, but also other diseases related to the prominent role of oxidative stress or inflammatory pathways, such as Alzheimer's disease.