Combination Therapy of Salvianolic Acid and Fluoxetine Improves the Cognitive Function of Rats with Chronic Stress-induced Depression

Abstract

To establish the beneficial effects of salvianolic acid and fluoxetine on the improvement of cognitive function and amelioration of depression-like symptoms of rats with chronic stress-induced depression. Ninety-nine male Sprague-Dawley rats were randomly divided into 5 groups--a control group with no stress challenge and 4 chronic stress groups. Rats assigned to chronic stress groups were exposed to stress for 3 weeks, and then were given placebo, fluoxetine (20 mg/kg), salvianolic acid (40 mg/kg), or combined fluoxetine and salvianolic acid. Body weight of each rat was recorded throughout the study. Sucrose preference test and water maze experiment were performed after chronic stress challenge and after drug treatment to assess the effect of drug treatments on depressive-like symptoms and cognitive function. The sucrose preference test was also performed before chronic stress exposure for baseline measurement. Exposure of rats to chronic stress for 3 weeks significantly reduced body weight and sucrose preference values compared with the no stress control. The water maze experiment showed that chronic stress impaired the spatial learning of rats as well. Treatment of stress-challenged rats with fluoxetine and fluoxetine combined with salvianolic acid resulted in shorter training latency and longer time spent in the target quadrant during the exploration stage of the water maze experiment compared with placebo treatment. Effect of the combined regimen was found more obvious. Combination therapy of salvianolic acid and fluoxetine could alleviate depression-like symptoms and cognitive deficit induced by chronic stress.