Pharmacological Evaluation of Antidepressant-Like Effect of Genistein and Its Combination with Amitriptyline: An Acute and Chronic Study.

Gaurav Gupta,Tay Jia Jia,Kamal Dua,Dinesh Kumar Chellappan,Lim Yee Woon,Mayuren Candasamy

doi:10.1155/2015/164943

Abstract

The present study was designed to evaluate the acute and chronic antidepressant effect of genistein in combination with amitriptyline in mice. Animals were divided into six groups (n = 6) for treatment with water, genistein, or amitriptyline, either alone or in combination for ten days. Animals were subjected to locomotor activity testing; tail suspension test (TST); and forced swim test (FST) and immobility time was recorded on day one and day ten. Acute treatment of all treatment groups did not significantly reduce the immobility time (p > 0.05). Chronic treatment of combination of genistein (10 mg/kg) and amitriptyline (5 mg/kg and 10 mg/kg) significantly reduced the immobility time as compared to control group (p < 0.001) and was comparable to amitriptyline alone (10 mg/kg). However, no changes in anti-immobility activity in combination of subeffective doses of genistein (5 mg/kg) and amitriptyline (5 mg/kg) were observed. Genistein at its standard dose (10 mg/kg) rendered synergistic effects in combination with subeffective dose of amitriptyline (5 mg/kg) and additive effects in combination with therapeutic dose of amitriptyline (10 mg/kg).

Highlights

Depression is the most common affective disorders; it may range from very mild conditions, bordering on normality, to severe depression accompanied by hallucinations and delusions
The emotional symptoms of depression described by Diagnostic and Statistical Manual of Mental Disorders are lack of interest, sadness, guiltiness, and suicidal thoughts while lack of sleep, headaches, pain, sleep disorders, changes in appetite, gastrointestinal disorders, and changes in psychomotor function are the physical symptoms of depression
We aimed to investigate the effect of genistein in combination with amitriptyline administered acutely and chronically on animal behaviour in tail suspension test (TST) and forced swim test (FST) and locomotor activity testing in mice

Summary

Introduction

Depression is the most common affective disorders (defined as disorders of mood rather than disturbances of thought or cognition); it may range from very mild conditions, bordering on normality, to severe (psychotic) depression accompanied by hallucinations and delusions. Around 6.3 to 15.7% of the world’s population is estimated to suffer depression once in life according to World Health Organization International Consortium of Psychiatric Epidemiology (WHOICPE). 7 to 12% in men and 20 to 25% in woman are the estimation of lifetime prevalence of major depression in adults [1, 2]. Tricyclic antidepressant like amitriptyline is chemically heterocyclic compounds used effectively for treating depression since it acts as a serotonin-norepinephrine reuptake inhibitor, thereby increasing the concentration of these transmitters in the synapse. Since many side effects due to chronic administration limit the therapeutic treatment, so it is necessary to unveil new targeted drugs with the claim of a more favourable tolerability and efficacy profile [3]

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