Abstract: The neurotransmitter histamine receives less attention compared with other biogenic amines, because of its moderate action in the central nervous system (CNS). Recent evidence suggests that histamine plays an important role in multiple CNS disorders, however histamine receptors in different cells may have distinct actions. So, we generated mice with selective deletion of histamine receptors in different types of neuron and glia to dissect the role of cell type specific histamine receptors in CNS disorders. We discovered that histamine H2/H3 receptors in neurons, H1/H2 receptors in astrocytes, H2 receptors in oligodendrocytes are implicated in the process of excitotoxicity, neuronal autophagy, glial scar formation and remyelination following cerebral ischemia. Recently, we found that deletion of H1 receptors in cholinergic neurons (Hrh1fl/fl;ChATCre), but not the glutamatergic (Hrh1fl/fl;CaMKII?Cre) or dopaminergic neurons (Hrh1fl/fl;DATCre), selectively leads to schizophrenia-like negative symptoms, suggesting H1R in cholinergic neurons could serve as a therapeutic target for the negative symptoms of schizophrenia. The in-depth understanding of the potential action of cell type specific histamine receptors are necessary stepping stones to unlock the wide-ranging applications of histamine related agents in the clinical arena.

Key words: cerebral ischemia, histamine, histamine receptor, schizophrenia