Altered histamine H3 receptor radioligand binding in post-mortem brain samples from subjects with psychiatric...

Histamine is a modulatory neurotransmitter in the brain. Auto- and hetero-histamine H3 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 H3 receptors in human brain may be affected in schizophrenia, bipolar disorder, major depression.

Histamine H3 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.

Compared with the controls, increased H3 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 H3 receptor radioligand binding were found in the temporal cortex. In hippocampal formation of control subjects, H3 receptor radioligand binding was prominent in dentate gyrus, subiculum, entorhinal cortex and parasubiculum. Decreased H3 binding was found in the CA4 area of bipolar subjects. Decreased H3 binding in CA2 and presubiculum of medication-free bipolar subjects was also seen.

The results suggest that histamine H3 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 H3 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.