Folic acid ameliorates depression-like behaviour in a rat model of chronic unpredictable mild stress

Abstract Background Depression is characterized by significant and low mood. Classical antidepressants are still not adequate in treating depression because of undesirable side effects. Folic acid, a member of the vitamin B complex, in considered to be strongly associated with the function and development of the central nervous system. Thus, in this study, we established a model of depression through chronic unpredictable mild stress (CUMS) in rats and assessed the antidepressant effects and mechanisms of folic acid. Methods Sprague–Dawley rats were randomly divided into four groups: control, chronic unpredictable mild stress (CUMS), CUMS treated with folic acid, and CUMS treated with citalopram. Rats were assessed in terms of weight change, open-field test and sucrose preference. Homocysteine, monoamine neurotransmitters, interleukin-6, brain-derived neurotrophic factor (BDNF), β-endorphin levels in the serum and brains of rats were analysed. Results Folic acid exhibited antidepressant-like effects in open-field and sucrose preference tests. Folic acid treatment effectively increased the levels of monoamine neurotransmitters, BDNF and β-endorphin, interleukin-6 and homocysteine levels were also significantly suppressed by folic acid administration. Conclusions These findings serve as preclinical evidence that folic acid plays an antidepressant-like role in several pathways involving monoamine neurotransmitters. Thus, folic acid may be used as a potential antidepressant.