Altered histamine H 3 receptor radioligand binding in post-mortem brain samples from subjects with psychiatric diseases

Abstract

Background and purpose: Histamine is a modulatory neurotransmitter in the brain. Auto- and hetero-histamine H 3 receptors are present in human brain and are potential targets of antipsychotics. These receptors may also display disease-related abnormalities in psychiatric disorders. Here we have assessed how histamine H 3 receptors in human brain may be affected in schizophrenia, bipolar disorder, major depression. Experimental approach: Histamine H 3 receptor radioligand binding assays were applied to frozen post-mortem prefrontal and temporal cortical sections and anterior hippocampal sections from subjects with schizophrenia, bipolar disorder, major depression and matched controls. Key results: Compared with the controls, increased H 3 receptor radioligand binding was found in dorsolateral prefrontal cortex of schizophrenic subjects (especially the ones who were treated with atypical antipsychotics), and bipolar subjects with psychotic symptoms. No differences in H 3 receptor radioligand binding were found in the temporal cortex. In hippocampal formation of control subjects, H 3 receptor radioligand binding was prominent in dentate gyrus, sublculum, entorhinal cortex and parasubiculum. Decreased H 3 binding was found in the CA4 area of bipolar subjects. Decreased H 3 binding in CA2 and presubiculum of medication-free bipolar subjects was also seen. Conclusions and implications: The results suggest that histamine H 3 receptors in the prefrontal cortex take part in the modulation of cognition, which is impaired in schizophrenic subjects and bipolar subjects with psychotic symptoms. Histamine H 3 receptors probably regulate connections between hippocampus and various cortical and subcortical regions and could also be involved in the neuropathology of schizophrenia and bipolar disorder. © 2009 The British Pharmacological Society All rights reserved.