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.%目的 研究氯胺酮与酒精对小鼠学习记忆的行为学及相关神经递质的影响.方法 40只小鼠分为4组:对照组、氯胺酮组、酒精组、氯胺酮酒精联合给药组,每组10只.氯胺酮和酒精分别采用腹腔注射和灌胃给药的方式,1次/d,连续14d.通过跳台和水迷宫实验检测各组小鼠的学习记忆能力,通过测定小鼠大脑组织中乙酰胆碱(acetylcholine,ACh)和5-羟色胺(5-hydroxy tryptamine,5-HT)的含量初步探讨氯胺酮与酒精对小鼠学习记忆的影响机制.结果 1(1)跳台实验:给药组小鼠均出现潜伏期缩短,错误次数增多(P＜0.05).与单独给药相比,联合给药组错误次数显著增加.(2)水迷宫实验:给药组小鼠潜伏期显著增加(P＜0.05),平台所在象限活动时间明显缩短(P＜0.05),穿台次数显著减少(P＜0.05).(3)生化指标测定:各给药组ACh和5-HT含量明显下降,且联合给药组较单独给药组下降更为明显(P＜0.05).结论 氯胺酮和酒精对小鼠学习记忆行为的抑制具有协同作用,这可能与共同抑制5-HT和ACh含量的降低有关.
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