In the eight-arm radial maze test, irradiated rats showed a deficit in working memory, which is also shown in schizophrenic patients. It has been suggested that adult neurogenesis may serve an important role in hippocampal dependent memory processes. First, exposure to an enriched environment or increased physical activity leads to increased hippocampal neurogenesis and improved spatial memory. Second, the comprehensive loss of hippocampal dependent memory function in old age is related to decreased neurogenesis. Taken together, it seems that cognitive impairment in irradiated rats may be due to reduction of hippocampal neurogenesis. In this study, we found that methamphetamine-induced hyperactivity was Senkyunolide-A significantly enhanced in the irradiated rats, suggesting Polyphyllin-II hyperdopaminergic activity. The precise mechanisms underlying the hyperdopaminergic states in irradiated rats could not be explained, as we found no alteration of dopamine or its major metabolite DOPAC in the irradiated rat brains. Since mesolimbic dopaminergic neurons innervate the SGZ of the dentate gyrus, the dopaminergic activities of these neurons may be involved in the regulation of hippocampal neurogenesis. Furthermore, we previously reported that cell destruction of dentate granules by intrahippocampal injection of colchicine enhanced methamphetamine-induced hyperactivity in rats, suggesting that dentate granule cells may regulate methamphetamine-induced behavioral changes. Taken together, the evidence suggests that the decrease in hippocampal neurogenesis by irradiation may, in part, be implicated in the hyperdopaminergic activity of irradiated rats although the cumulative numbers of granule cells in the granule layer were not altered in irradiated rats. Accumulating evidence suggests that hypofunction of the NMDA receptors may play a role in the pathophysiology of schizophrenia. However, we did not find any alteration in dizocilpine-induced hyperactivity and levels of amino acids related to NMDA receptor neurotransmission in irradiated rat brains.The total numbers of BrdU-positive cells in both SVZ and SGZ were significantly lower than those of sham-irradiated rats three months after fractionated irradiation. The static BrdU-positive cell count may reflect neurogenesis and/or survival of the recent born cells.