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

本研究旨在建立注意力缺陷多动障碍（ADHD）模型，以确定产前暴露于甲基偶氮氧甲醇乙酸酯（MAM）或新生儿海马损伤的大鼠海马形态异常与行为指标之间的关系。在断乳期或成年期对大鼠进行旷场、梭箱回避和径向迷宫学习试验，结果如下：1）在妊娠第13或15天（G）给予MAM的大鼠在断奶期表现出多动性，但在成年期没有表现出多动性。2）G13和G15 MAM大鼠表现出易化的回避学习，而G17和G19 MAM大鼠与对照组相比表现出回避学习的障碍。3）G13和G15 MAM大鼠在8臂径向迷宫上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学习缺陷，4）在径向臂迷宫保持任务中，当保持间隔为10 min或更长时，G13 MAM大鼠显示工作记忆受损，5）出生当天海马损伤的大鼠在八臂迷宫中表现出位置学习缺陷。在MAM大鼠中表现出多动、易化回避和空间学习缺陷的模型动物伴有海马形态学异常（偶尔的CA 1锥体层破坏和/或大量的异位锥体神经元团）。提示ADHD综合征可能与围产期海马功能障碍有关。

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.