Abstract: Objective To study the effects of ketamine and alcohol on learning and memory in mice and its possible mechanism. Methods Forty mice were divided into 4 groups： normal control group, ketamine group, alcohol group, and alcohol plus ketamine group. Ketamine and alcohol were given by intraperitoneal injection and intragastric administration, respectively, 1 time per day, for 14 days. The ability of learning and memory in mice was tested by the method of step-down and Morris water maze. Acetylcholine（ACh） and 5-hydroxy tryptamine（5-HT） in mice brain tissue were analyzed for the possible mechanism. Results （1） Step-down： The treatment groups lessened the latency and added wrong times（P＜0.05）. The number of errors in the combined treatment group significantly increased comparing with the single drug treatment group（P＜0.05）. （2） Morris water-maze： The treatment groups prolonged the latency（P＜0.05）, reduced the target quadrant activity time significantly（P＜0.05）, and decreased the numbers of crossing the former platform significantly（P＜0.05）. （3） Biochemical index determination： The concentrations of ACh and 5-HT in treatment groups decreased significantly（P＜0.05）, showed a more decreasement comparing with the single drug treatment group. Conclusion Ketamine has a synergistic effect with alcohol on learning and memory impairment in mice, which may be related to the common inhibitive effect on the ACh and 5-HT.

Key words: forensic toxicology, ketamine, alcohol, learning, memory, mice