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Subject Area

Clinical Pharmacology

Article Type

Original Study

Abstract

Objective This study aimed to investigate the antidepressant effect of simvastatin in the hydrocortisone model of depression. Background Depression is considered the most common psychiatric disorder that causes disability in our life. It puts a heavy burden on both human and society. Simvastatin therapy alone or with selective serotonin reuptake inhibitors has shown desirable effects in the treatment of depression. Material and methods Rats were divided into five groups treated for 3 weeks as follows: control group, hydrocortisone group received intraperitoneal injection of hydrocortisone 40 mg/kg/day to induce depression, fluoxetine group received fluoxetine 10 mg/kg/day orally in addition to hydrocortisone, simvastatin group received simvastatin 10 mg/kg/day orally in addition to hydrocortisone, and combination group received fluoxetine 10 mg/kg/day and simvastatin 10 mg/kg/day in addition to hydrocortisone. During the experiment, behavioral tests were done in addition to biochemical assessment in the hippocampal tissue. Results Hydrocortisone administration caused significant increase in immobility time in forced swim test, significant decrease in sucrose preference percentage in sucrose preference test, significant decrease in hippocampal brain-derived neurotrophic factor and serotonin, significant increase in hippocampal malondialdehyde, and significant decrease in hippocampal reduced glutathione. Treatment with fluoxetine and simvastatin showed a significant decrease in immobility time in forced swim test, significant increase in sucrose preference percentage in sucrose preference test, significant increase in hippocampal brain-derived neurotrophic factor and serotonin, significant decrease in hippocampal malondialdehyde, and significant increase in hippocampal glutathione. Conclusion Simvastatin alone or with fluoxetine could be a promising drug in the treatment of depression.

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