Creatine and α-Lipoic Acid Improved Depressive Behavior Induced by Interferon-α in Mice: Malondialdehyde Level Remained Unchanged

Objective: Interferon-alpha (IFNa) is a cytokine with various biological roles but it may induce psychological adverse effects. Introducing alternative medicine is essential to prevent this side effect. This study was performed to determine the antidepressant effects of creatine (Crt) and α-lipoic acid (ALA). 
Materials and Methods: Female albino mice (6–8 weeks old) were used. IFNa (16×105 IU/kg/day, SC), Crt (5 and 10 mg/kg, gavage feeding tube), and ALA (20 and 40 mg/kg, IP) were administered for 6 days. After the locomotor test, behavioral parameters of depression, including immobility during the forced swimming test (FST), and finally serum malondialdehyde (MDA) were measured as factors for oxidative stress. 
Results: There was not important difference regarding the locomotor test. Crt 5 mg/kg and ALA 40 mg/kg when administered alone reduced the immobility time during FST when compared with the control groups (75±15 and 82±16 s, respectively, P < 0.05). Crt 5 mg/kg and IFN co-administration reduced the immobility time to 108±23 s, which was lower than that of the IFNa alone group (156±8 s, P < 0.05). Administrating ALA 40 mg/kg and IFNa together showed same results (95±11 s vs. IFNa alone group, P < 0.01). The results of measuring MDA did not show noticeable difference. 
Conclusion: In general, improvement of behavioral parameters in mice treated with Crt and ALA indicates a clear effect of these two compounds in modulating mood and depressive behaviors. Although MDA level differences were not observed, Crt and ALA modulation in the neurotransmitter system may be involved in their antidepressant effects.