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Objective Alzheimers disease (AD) is a progressive neurodegenerative disorder which mainly manifests as severe impairments of learning and memory.One prominent pathological hallmark in AD patients brain is the presence of high density of senile plaques composed of β-amyloid peptide (Aβ).Type 2 diabetes mellitus is a risk factor of AD, most likely linked to an impairment of insulin signaling in the brain.Liraglutide, a novel long-lasting Glucagon-like peptide-1 (GLP-1) analogue, facilitates insulin signaling and shows neuroprotective properties in vitro and in vivo.However, it is still lack of behavioral evidence of the protection effect of Liraglutide against Aβ-induced impairment of spatial cognition.Methods The present study observed the effects of bilateral intrahippocampal injection of Liraglutide on spatial learning and memory in the Morris water maze test and investigated the potential protective function of Liraglutide against Aβ-induced memory impairment.Results (1) Bilateral intrahippocampal injection of Aβ 25-35 (4 nmol) resulted in a significant decline of spatial learning and memory; (2) Liraglutide (5 nmol) alone slightly improved the learning and memory, but there is no significant differences compared with control groups; (3) Pretreatment with 0.5 nmol or 5 nmol, but not 0.05 nmol, Liraglutide effectively reversed the impairment of spatial learning and memory induced by Aβ25-35; (4) All drugs used in the present experiments did not affect the vision and motor function of the rats.Conclusion Aβ25-35 could result in a significant decline of spatial learning and memory of rats and pretreatment with Liraglutide could effectively prevent the impairment induced by neurotoxic Aβ25-35.Thus, these results suggest that insulin signaling in the brain maybe a new strategy to ameliorate learning and memory impairment in AD.