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Ghrelin is an orexigenic hormone mainly produced by the stomach and released into the circulation.Ghrelin receptors (GHSR1a) are enriched in hippocampus, suggesting that it may play certain roles in hippocampus-dependent learning and memory.However, since GHSRla is expressed in numerous brain regions,ghrelin/GHSR1a signaling may involved in divergent neuronal functions, which makes the interpretation of ghrelin on learning and memory complicated.To dissect the effect of ghrelin on hippocampus-dependent memory acquisition, we locally infused ghrelin (5 pmol, 0.5 μL) or same volume of vehicle into CA1 of dorsal hippocampus 20 min before training.We then investigate the performace of two groups of mice on a battery of hippocampus-dependent learning and memory task, including object location memory task, Morris water maze,contextual fear conditioning.Surprisingly, to the contary of previous reports, our present results consistenly showed that (1) ghrelin impairs object location memory while had no effect on new object recognition performance, and this impairment in object location memory was reversed by GHSR1 a antibody and Pl3-Kinase inhibitor.(2) local infusion of ghrelin causes learning deficit in water maze.Importantly, such dose of ghrelin has no observable effect on anxiety of tested animals.Altogether, our finding indicates that ghrelin blocks the acquisition of hippocampus dependent learning and memory, which is opposite to previous reports.Further study are need to explore the underlying mechanisms.