Folic acid ameliorates anxiety and depressive like behavior induced by nicotine withdrawal through restoration of behavioral and biochemical alterations in adolescent male rats.

INTRODUCTION: The present study aimed to assess the efficacy of folic acid (FA) on withdrawal following nicotine (Nic) administration in adolescent male rats.

METHODS: Adolescent male rats were divided into two groups: 1) vehicle and 2)Nic (Nic-2mg/kg), and were under the 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 (15mg/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 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.

CONCLUSION: The present findings suggest anxiety and depression caused by Nic withdrawal were attenuated by FA more likely through reduction activity of MAO, the important enzyme responsible for serotonin metabolism along with balance between oxidant/anti-oxidant 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. Folic acid supplementation as well as bupropion improved cognitive disorders induced by Nic withdrawal by increasing neuro-inflammation, neuro-oxidative damage.