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Histamine does not only modulate the immune response and inflammation, but also acts as a neurotransmitter in the mammalian brain. The histaminergic system plays a significant role in the maintenance of wakefulness, appetite regulation, cognition and arousal, which are severely affected in neuropsychiatric disorders. In this review, we first briefly describe the distribution of histaminergic neurons, histamine receptors and their intracellular pathways. Next, we comprehensively summarize recent experimental and clinical findings on the precise role of histaminergic system in neuropsychiatric disorders, including cell-type role and its circuit bases in narcolepsy, schizophrenia, Alzheimer's disease, Tourette's syndrome and Parkinson's disease. Finally, we provide some perspectives on future research to illustrate the curative role of the histaminergic system in neuropsychiatric disorders.
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