The efficacy of Vitamin B6 and alpha-lipoic acid in preventing levetiracetam depressant-like behavior in mice

Abstract

Background: Some antiepileptic drugs for instance levetiracetam cause depression in patients. Vitamin B6 is a cofactor involved in the neurotransmitter synthesis. α-Lipoic acid (ALA) is a mitochondrial cofactor that can prevent neuronal damage. The aim of this study was to evaluate the effectiveness of B6 and ALA for preventing levetiracetam depression in mice. Methods: Male NMRI mice (weighing 25 ± 3 g) were used. Levetiracetam (20 mg/kg), and pretreatments with ALA (20, 40 mg/kg), Vitamin B6 (100 mg/kg), or imipramine (10 mg/kg) as the control positive were all administered intraperitonealy for 14 consecutive days. The locomotor test and forced swimming test (FST) were performed on days 7 and 15 on same groups of animals, novelty suppressed feeding test (NSFT) was tested on day 16. Results: Immobility time in FST increased following levetiracetam administration (day 7, 166 ± 5.63s vs. control 135 ± 9.9s, P = 0.020; day15, 188 ± 6.45s vs. control 150 ± 9.55s, P = 0.0326). Pre-treatment with B6 significantly reduced the immobility time during FST (day 7, 109 ± 16.4s, P < 0.001; day 15, 124 ± 12s, P < 0.001 vs. levetiracetam alone), these changes were similar to imipramine, treatments did not change the locomotor activity. However, following ALA pre-treatment, the locomotor activity declined and neither of ALA doses reduced immobility time during FST. During NSFT, pre-treatment with B6, and ALA similar to imipramine decreased latency; B6 and ALA 20 mg/kg increased food intake compared to levetiracetam alone. Conclusion: While B6 pretreatment clearly prevented depressive-like behavior induced by levetiracetam, ALA 20 mg/kg showed antidepressant-like effect only in NSFT. Supplements are recommended for further evaluation to prevent depression comorbidity of antiepileptic drugs. © 2022, Faculty of Pharmaceutical Sciences, Chulalongkorn University. All rights reserved.