Neuropharmacological Evaluation Of Synergistic Antidepressant Efficacy Of Imipramine And Bacopa Monnieri In Rat Models Of Behavioral Despair And Oxidative Neurotoxicity

Abstract

Background: Depression is a multifactorial neuropsychiatric disorder in which both monoaminergic dysfunction and oxidative stress play critical roles. Although tricyclic antidepressants like imipramine are clinically effective, their use is limited by delayed onset and adverse effects. Bacopa monnieri, an Ayurvedic herb, possesses antioxidant and neuroprotective properties that may complement the action of conventional antidepressants.

Objective: The present study aimed to evaluate the synergistic antidepressant efficacy of imipramine in combination with Bacopa monnieri in rat models of behavioral despair and oxidative neurotoxicity.

Methods: Hydroalcoholic extract of Bacopa monnieri was authenticated and subjected to preliminary phytochemical screening. Adult male Wistar rats were divided into six groups (n=6) and treated for 14 days: vehicle control, imipramine (15 mg/kg), Bacopa monnieri (100 and 200 mg/kg), and combinations of imipramine with Bacopa monnieri. Behavioral assessments were performed using the forced swim test (FST) and tail suspension test (TST), followed by locomotor activity measurement. Oxidative stress markers including malondialdehyde (MDA), superoxide dismutase (SOD), catalase, and reduced glutathione (GSH) were estimated in brain homogenates. Histopathological examination of hippocampal sections was also carried out. 

Results: Phytochemical analysis confirmed the presence of bacosides, saponins, and flavonoids. Combination therapy significantly reduced immobility time in FST and TST compared to individual treatments, without altering locomotor activity. Biochemical assays showed decreased lipid peroxidation and restoration of antioxidant enzymes, while histopathology revealed improved neuronal integrity in the combination groups.

Conclusion: The synergistic use of imipramine and Bacopa monnieri offers enhanced antidepressant efficacy and neuroprotection by modulating monoaminergic and oxidative stress pathways. This combination may represent a promising therapeutic approach for managing depression.