Memory deficits with aging are related to the neurodegeneration in the brain,including a reduction in arginine vasopressin (AVP) in the brain of patients with Alzheimer\'s disease (AD).AVP(4-8),different from its precursor AVP,plays memory enhancement roles in the CNS without peripheral side-effects.However,it is not clear whether AVP(4-8) can improve cognitive behaviors and synaptic plasticity in the APP/PS1 mouse model of AD.Here,we investigated for the first time the neuroprotective effects of AVP(4-8) on memory behaviors and in vivo long-term potentiation (LTP) in APP/PS 1-AD mice.The results showed that: (1) APP/PS1-AD mice had lower spontaneous alternation in the Y-maze than wild-type (WT) mice,and this was significantly reversed by AVP(4-8);(2) the prolonged escape latency of APP/PS1-AD mice in the Morris water maze was significantly decreased by AVP(4-8),and the decreased swimming time in target quadrant recovered significantly after AVP(4-8) treatment;(3) in vivo hippocampal LTP induced by high-frequency stimulation had a significant deficit in the AD mice,and this was partly rescued by AVP(4-8);(4) AVP(4-8) significantly up-regulated the expression levels of postsynaptic density 95 (PSD95) and nerve growth factor (NGF) in the hippocampus of AD mice.These results reveal the beneficial effects of AVP(4-8) in APP/PS1-AD mice,showing that the intranasal administration of AVP(4-8) effectively improved the working memory and long-term spatial memory of APP/PS1-AD mice,which may be associated with the elevation of PSD95 and NGF levels in the brain and the maintenance of hippocampal synaptic plasticity.