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Patients with Alzheimer's disease (AD) always have cognitive impairments. In this study we investigated whether 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) has improvements on cognitive dysfunction. The scopolamine model of dementia was used to investigate the anti-amnesic activities of SKF83959, and then, Western blotting and pharmacological inhibitor were used to assay the anti-amnesic mechanisms of SKF83959. It was found that SKF83959 administration significantly improved the scopolamine-induced memory impairments in the passive avoidance task, Y-maze test, and Morris water maze task. Moreover, SKF83959 treatment significantly antagonized the down-regulating effects of scopolamine on brain-derived neurotrophic factor (BDNF) signaling cascade in the hippocampus, but not cortex. Importantly, the usage of K252a, a selective inhibitor of tyrosine kinase B (TrkB), significantly attenuated the protective effects of SKF83959 in the scopolamine model. Collectively, this study shows that SKF83959 has beneficial effects in the scopolamine model of dementia by modulation of hippocampal BDNF signaling, implying a novel and potential therapeutic agent for treating dementia in AD.Key words brain-derived neurotrophic factor; memory; scopolamine; SKF83959 As a world-wide neurodegenerative disease, Alzheimer's disease (AD) causes huge damage to our society.1) In clinical, patients with AD always have dementia, meaning the loss of memory.2,3) Dementia is very common in older persons, and leads to severe interference in occupational and social performance. Current researches have revealed that patients with AD have severe cholinergic dysfunction in the brain, [4][5][6] and some cholinergic antagonists, especially scopolamine, have been shown to induce memory impariments in rodents. 7) In contrast, some acetylcholinesterase inhibitors (AChEIs), such as donepezil, were developed for AD therapy in clinical. However, current AChEIs used clinically have various adverse effects including diarrhea, insomnia and vomiting, and their efficacy are not very good.8) Therefore, developing novel therapeutic agents to treat dementia in AD is very necessary.6-Chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) is one compound which belongs to benzazepine family and has been acknowledged as a selective D 1 -D 2 heteromer agonist. Until now, a lot of reports have been showing the effects of SKF83959 on the brain. For example, Wu et al. showed that SKF83959 has protective effects against neuroinflammation. 9)Chu et al. reported that SKF83959 has promoting effects on neuronal release of glutamate. 10) Zhang et al. found that SKF83959 administration has beneficial and reversing effects in the 6-hydroxy-dopamine (6-OHDA) model of Parkinson's disease. 11) We noticed that in 2014, Jiang et al. demonstrated the antidepressant effects of SKF83959 in mice which were mediated through activating the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (Tr...