The Administration of Melatonin Improved Depressive Behavior in Both Maximal Electroshock Seizure-Prone and Non-Seizure Mice After Undergoing Levetiracetam Treatment Publisher



Mesripour A ; Mobarakshahi A ; Rabbani M
Source: Turkish Journal of Pharmaceutical Sciences Published:2025

Abstract

Objectives: Comorbid psychiatric disorders, especially depression, pose challenges in epilepsy. Antiepileptic drugs, including levetiracetam, can also have psychiatric adverse effects, necessitating strategies to address mood regulation. The study aims to assess the impact of melatonin administration on depressive behavior in epileptic and non-epileptic mice. Materials and Methods: Male albino mice were assigned to different treatment groups. Levetiracetam (20 mg/kg ip) was injected for 14 days; melatonin (25 mg/kg ip) was injected for 7 days. Additional groups were included for epileptic mice. Maximal electroshock was used to induce seizures: locomotor activity, immobility time in the forced swimming test (FST), latency, and food consumption were measured in the novelty-suppressed feeding test (NSFT). Results: There were insignificant differences in locomotor activity between groups. In the FST, levetiracetam administration significantly increased the immobility duration compared to the control group in epileptic and non-epileptic mice (p<0.05). The immobility duration in the levetiracetam-melatonin groups of both epileptic and non-epileptic mice significantly decreased compared to the levetiracetam alone group (p<0.01). In NSFT, the levetiracetam group exhibited a significantly longer latency (p<0.01) and less food intake (p<0.05) compared to the control group; these changes were reversed when levetiracetam-melatonin was administered. In epileptic groups, the difference in latency was insignificant, while food consumption increased significantly (p<0.05) in the levetiracetam-melatonin group compared to the levetiracetam-alone group. The results observed with melatonin were similar to those of imipramine. Conclusion: Melatonin was found to reduce depressive behavior in both non-epileptic and epileptic groups. These results suggest that melatonin could be a potential therapeutic agent for countering the depressive effects of levetiracetam. © 2025 The Author. Published by Galenos Publishing House on behalf of Turkish Pharmacists’ Association.