ghrelininduced hippocampal neurogenesis and enhancement of cognitive function are mediated independently of ghigf1 axis lessons from the spontaneous dwarf rats we recently have reported that ghrelin modulates adult hippocampal neurogenesis however there is a possibility that the action of ghrelin on hippocampal neurogenesis could be in part due to the ability of ghrelin to stimulate the ghinsulinlike growth factor igf1 axis where both gh and igf1 infusions are known to increase hippocampal neurogenesis to explore this possibility we assessed the impact of ghrelin on progenitor cell proliferation and differentiation in the dentate gyrus dg of spontaneous dwarf rats sdrs a dwarf strain with a mutation of the gh gene resulting in total loss of gh double immunohistochemical staining revealed that ki67positive progenitor cells and doublecortin dcxpositive neuroblasts in the dg of the sdrs expressed ghrelin receptors we found that ghrelin treatment in the sdrs significantly increased the number of proliferating cell nuclear antigen and brdulabeled cells in the dg the number of dcxlabeled cells in the dg of ghrelintreated sdrs was also significantly increased compared with the vehicletreated controls to test whether ghrelin has a direct effect on cognitive performance independently of somatotropic axis hippocampusdependent learning and memory were assessed using the ymaze and novel object recognition nor test in the sdrs ghrelin treatment for 4 weeks by subcutaneous osmotic pump significantly increased alternation rates in the ymaze and exploration time for novel object in the nor test compared to vehicletreated controls our results indicate that ghrelininduced adult hippocampal neurogenesis and enhancement of cognitive function are mediated independently of somatotropic axis