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OBJECTIVE Age-related emotional memory deficit is an important complication with cognition decline in Alzheimers disease and aged individuals.However, little is known about the underlying mechanism.METHODS By using electrophysiological recording,western blotting and behavior experiment, we examined the role of norepinephrine (NE) and its reuptake inhibitor desipramine in the regulation of rat hippocampal long-term potentiation (LTP), surface expression of AMPA receptor (AMPAR), and associative fear memory in contextual fear conditioning.RESUILS We found there was a defective regulation of NE content and AMPAR trafficking during fear conditioning in aged rats, which were accompanied by impaired emotional memory and LTP,when compared with adult rats.Furthermore, we also found that exogenously upregulating NE level ameliorated the impairment of LTP and emotional memory via enhancing AMPAR trafficking in aged rats.Conversely,the downregulation of NE function impaired hippocampal LTP in adult rats.Finally, acute treatment with NE or desipramine rescued the impaired emotional memory in aged rats.CONCLUSION These findings imply a pivotal role for NE in synaptic plasticity and associative fear memory in aging, and suggest that desipramine may be a potential candidate for the therapy of age-related emotional memory deficit.