A neurobehavioral study of experimentally-induced model animals of attention-deficit hyperactive disorders (ADHD)

为了建立注意缺陷多动障碍(ADHD)模型，研究了胎儿期暴露于甲氧基甲醇醋酸酯(MAM)的大鼠海马区形态异常与行为学指标的关系及新生大鼠海马区损伤的关系。对大鼠在断奶和成年期分别进行了旷场、穿梭箱回避和放射状迷宫学习试验。结果表明：1)孕龄13天和15天的MAM大鼠在断奶阶段表现为多动，而G13和G15 MAM大鼠表现出回避学习，而G17和G19 MAM大鼠则表现出回避学习障碍；3)G13和G15 MAM大鼠在8臂迷宫的位置学习任务中表现出学习缺陷，但在线索学习任务中没有表现出明显的学习障碍。4)G13 MAM大鼠在径向臂迷宫保持任务中保持时间间隔大于或等于10min时，表现出工作记忆障碍；5)出生当天损毁海马区的大鼠在8臂径向迷宫中表现出位置学习障碍。MAM大鼠表现出多动、易回避和空间学习障碍的模型动物表现为海马区形态异常(偶有CAL锥体层破坏和/或大量异位锥体神经元团)，这些行为障碍似乎与ADHD儿童相似。我们的发现表明ADHD综合征可能是由于围产期发生的海马区功能障碍所致。

Studies were performed to determine the relation between the morphological abnormalities of the hippocampus and the behavioral indices in rats exposed to prenatal methylazoxymethanol acetate (MAM) or with neonatal hippocampal lesions, in attempts to produce a model of attention-deficit hyperactive disorders (ADHD). Rats were subjected to a open-field, a shuttle-box avoidance and a radial maze learning tests during weaning or adult period.Result were follows : 1) Rats treated MAM on the day 13 or 15 of gestation (G) showed hyperactivity at the weaning stage, but not at the adult period, 2) The G13 and G15 MAM rats showed a facilitated avoidance learning, whereas the G17 and G19 MAM rats showed a disability of avoidance learning compared to the controls, 3) The G13 and G15 MAM rats showed a learning deficit in the place-learning task but not in the cue-learning task on a 8-arm radial maze, 4) The G13 MAM rats showed an impairment of working memory when the retention interval was 10 min or more on a radial-arm maze retention task, 5) Rats lesioned the hippocampus on the day of birth showed a place-learning deficit on a 8-arm radial maze. Model animals which showed a hyperactivity, a facilitated avoidance and a spatial learning deficit in MAM rats tad mophological abnormalities of the hippocampus (occasional disruptions of the CAl pyramidal layer and/or numerous ectopic pyramidal neuron mass).These behavioral disorders seem to be similar to those in ADHD children. Our findings indicate that the ADHD syndrome might be caused by hippocampal dysfunction which was occurred during perinatal period.