Effects Of Ketamine On Learning And Memory Impairment Induced By Ethanol And Its Mechanisms In Mice

Objective: To study the effects of ketamine on learning and memory impairmentinduced by ethanol in mice and investigate its possible mechanism.Methods: A total of120male mice were divided into4groups: a normal controlgroup, a ketamine group, an ethanol group and an ethanol plus ketamine group.10miceeach group in every experiment. Ketamine and ethanol were respectively taken byintraperitoneal injection and oral administration,1/d, for14d. The ability of learning andmemory in mice was tested by the way of step-down and Morris water maze. Ach,5-HTand TChE in mice brain tissue were determined for the possible mechansim; Thepathological changes of hippocampus were observed by HE stain; The expressions ofCREB、PKA and AC gene in hippocampus were detected by RT-PCR; The expressions ofpCREB/CREB were detected by western blot method.Results:(1)The combined treatment group prolonged the latency and improvedwrong times(P﹤0.05) in step-down. Meanwhile it prolonged the escape latency (P﹤0.05)and reduced the target quadrant activity time and the number of mice crossing the formerplatform significantly(P﹤0.05) in Morris water-maze, which proved that the abilty ofSpatial learning and memory in them was impaired.(2)The content of ACh and5-HTreduced obviously (P﹤0.05), and the activity of TChE improved in mice’ hippocampus intreatment groups (P﹤0.05).(3)After the combined treatment with ketamin and ethanol,CREB、PKA and AC mRNA were down regulated by RT-PCR （P<0.05）, andpCREB/CREB were down regulated by western blot（P<0.05）.Conclusion: The data indicate that combination of ketamine and ethanol is synergic inthe inhibition of learning and memory in mice, its mechanisms may be related to the CREBsignal transduction pathway and the related neurotransmitter.