Alpha-lipoic acid attenuates depressive symptoms in mice exposed to chronic unpredictable mild stress

Abstract

Background: Depression is the most common psychiatric illness that involves mood disturbances affecting many brain regions. Despite many approaches available to treat depression, only about 35% of depressed patients achieve remission upon receiving antidepressants. Alpha-lipoic acid (ALA) is an antioxidant that plays an essential role in mitochondrial energy metabolism and neurotransmitter modulation. Hence, this research was aimed at assessing a possible antidepressant effect of ALA in mice exposed to chronic unpredictable mild stress (CUMS).

Methods: Twenty-five (25) Swiss albino mice weighing between 20-26 g were grouped into five groups of five mice each (n=5). Group 1: which served as control received normal saline (NS) and was exposed to CUMS, Groups 2, 3, and 4 received graded doses of ALA (100, 200, and 400 mg/kg respectively), Group 5 (positive control) received fluoxetine (20 mg/kg). Daily administration was done through oral gavage. The animals were subjected to open field (OF) and staircase (SC) tests after induction of depression using CUMS. Thereafter, brain and blood samples of the mice were collected for serotonin, brain-derived neurotrophic factor (BDNF), catalase, superoxide dismutase (SOD), and malondialdehyde (MDA) analysis.

Results: Treatment with ALA 200 mg/kg significantly decreased immobility time compared to CUMS + NS group (P≤0.05) in the tail suspension test. Similarly, fluoxetine 20 mg/kg significantly increased brain serotonin level and decreased BDNF level compared to CUMS + NS group (P≤0.05). However, ALA did not significantly affect brain serotonin and BDNF levels (P>0.05). In the OF test, a significant decrease was observed in the number of line crossings in ALA 100, 200, and 400 mg/kg and fluoxetine 20 mg/kg administered groups when compared with CUMS + NS group (P≤0.05). However, in SC test and oxidative stress biomarkers, no significant effect was observed (P>0.05).

Conclusion: ALA showed a promising antidepressant-like effect in mice subjected to CUMS murine model of depression by decreasing immobility time.