The neurobehavioral study of the attention-deficit/hyperactivity disorder (ADHD) model rats with abnormal morphogenesis of the hippocampus or the cerebellum

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We examined the correlation of the behavioral disorders with the morphogenetical abnormality of the brain in the attention-deficit/hyperactivity disorder (ADHD) model animals which were induced by methylazoxymethanol (MAM) injection on the prenatal 15-day (MAM-15 group) or 19-day (MAM-19 group).Behaviorally, 1) the MAM-15 rat showed a hyperactive tendency and the MAM-19 rat showed a hypoactive tendency during dark phase in a home-cage compared with the control rats, although no statistical difference among the groups was found in the open-field activity, during weaning, juvenile and adult periods, 2) the MAM-15 rat showed a facilitated avoidance and the MAM-19 rat showed a retarded avoidance in the shuttle-box avoidance learning situation during adulthood, but not during juvenile period, 3) the MAM-15 rat showed a severe impaired spatial cognition in the radial-maze and the Morris-type water maze learning situations, although the MAM-19 rat showed a moderate deficit, during each developmental stage. The behavioral disorder obtained in the MAM-15 rat correlated with a morphological abnormality of the hippocampus (disruption of the CA1 pyramidal layer and ectopic neuron mass), and the behavioral disorder obtained in the MAM-19 rat correlated with a disorder in foliation of the anterior cerebellum, which were histologically observed in these groups. Our behavioral and histological results suggest that the ADHD-like behavioral disorder may be derived from the hippocampal dysfunction induced by abnormal morphogenesis of the hippocampus.