Effects Of Docosahexenoic Acid On Learning And Memory Dysfunction Induced By Chronic Ketamine Exposure

Abstract:Objective:The aims of this study are to evaluate systematically the effects of docosahexenoic acid on learing and memory dysfunction induced by chronic ketamine exposure in ICR mice. The date of our study will provide objective information for Clinical treatment of chronic learning and memory dysfunction induced by chronic ketamine exposure.Methods:In our study, ketamine was administered Subcutaneous injection twice per day, each dose is30mg/kg, at the same time, the same volume of saline was given as control.30days after ketamine administration, the spatial learning and memory ability of ICR mice was evaluated by using Morris water maze. Then ketamine+DHA group and saline+DHA group mice were fed with docosahexaenoic acid (420mg/kg/d) for40days, meanwhile ketmine+saline group and saline+saline group mice were fed with the same volume of saline, the spatial learning and memory ability of ICR mice was evaluated again. Finally, density of glutamate and gamma-aminobutyric acid in hippocampus and prefrontal cortex was detected by high performance liquid chromatography.Results:(1) In the first Morris water maze test, ketamine treated mice needed a significantly longer escape latency compared with saline treated mice to find the platform (P=0.001) on day4of hidden-platform acquisition training; the number of target crossing for ketamine treated mice was significantly less than saline treated mice (P=0.010), the percentage of time in the target quadrant for ketamine treated mice was significantly less than control group mice(P=0.002), meanwhile the duration of the ketamine treated mice in opposite quadrant was significantly longer than control group mice(P=0.002).(2) In the second Morris water maze test, the escape latency of ketamine+saline group mice was significantly longer than ketamine+DHA group(P=0.036), saline+saline group (P<0.001) and saline+DHA group (P<0.001) on day4of hidden-platform acquisition training (P=0.036); while there were no significant group differences for four groups mice in spatial probe trail.(3) Gamma-amino butyric acid Concentration in hippocampus and prefrontal cortex of ketamine+saline group mice was significant higher than other three groups(P<0.05); there was no significant differences for four groups mice in glutamate density in hippocampus and prefrontal cortex.Conclusion:Chronic ketamine exposure leads to spatial learning and memory dysfunction in ICR mice, docosahexaenoic acid possibly can improve this spatial learning and memory dysfunction to some extent, and this positive effect of docosahexaenoic acid may be related to reduction of the high density of the gamma-amino butyric acid in the hippocampus and prefrontal cortex.