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Backgrounds: Depression is among the most frequent psychiatric comorbid conditions in Alzheimer's disease (AD). However, pharmacotherapy for depressive disorders in AD is still a big challenge current antidepressants used clinically, such as monoamine antidepressants, have shown only modest or little clinical bene ts. Here we investigated the mechanism of the interactions between depression and AD, which we believe would aid in the development of pharmacological therapeutics for the comorbidity of depression and AD.Methods: Female APP/PS1/Tau triple transgenic (3×Tg-AD) mice at 20 months of age and age-and gender-matched wild-type (WT) mice were used. The shuttle-box passive avoidance test (PAT), the open eld test (OFT), and the tail suspension test (TST) were implemented to assess behavioral changes. Highperformance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was used to detect the level of neurotransmitters related to depression in the hippocampus of mice. The data was identi ed by orthogonal projections to latent structures discriminant analysis (OPLS-DA). The expression of relative receptors was detected using Western blot.
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