Folic Acid Ameliorates Anxiety- and Depressive-Like Behavior Induced by Nicotine Withdrawal Through Restoration of Behavioral and Biochemical Alterations in Adolescent Male Rats

Abstract

Abstract Background The present study aimed to assess the efficacy of folic acid (FA) on withdrawal following nicotine (Nic) administration in adolescent male rats. Aims and Methods Adolescent male rats were divided into two groups: (1) vehicle and (2) Nic (Nic-2 mg/kg), and were under treatment from 21 to 42 days of age. After that, they continued the experiment without treatment and returned to a regular diet, except for one of those who received Nic. The rats were divided into four groups where they were treated with different doses of FA (5, 10, and 15 mg/kg) and bupropion (Bup) by oral gavage, and the final group included normal rats that received only FA (15 mg/kg) from 42 days of age for three weeks during which withdrawal occurred. Results Results showed that adolescent Nic exposure exacerbated the behavioral indices of anxiety- and depression-like behaviors, while FA attenuated the effects of Nic withdrawal on anxiety and depression as well as Bup. In support, the biochemical results demonstrated a balance between oxidant and antioxidant mediators in addition to the increase and decrease of serotonin and monoamine oxidase (MAO) activity in cortical tissue. TNF-α as an inflammatory agent was decreased, whereas IL-10 as an anti-inflammatory parameter was increased. Conclusions The present findings suggest anxiety and depression caused by Nic withdrawal were attenuated by FA more likely through the reduction activity of MAO, the important enzyme responsible for serotonin metabolism along with balance between oxidant/antioxidant and pro-inflammatory/anti-inflammatory mediators. However, various mechanisms might be involved, which requires further investigation. Implications Nic withdrawal-induced depression and anxiety like behavior in rats followed by neuro-oxidative damage and neuro-inflammation. FA supplementation as well as Bup improved cognitive disorders induced by Nic withdrawal by increasing neuro-inflammation and neuro-oxidative damage.