期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 157, 期 1, 页码 118-129出版社
WILEY
DOI: 10.1111/j.1476-5381.2009.00149.x
关键词
histamine H-3 receptor; schizophrenia; bipolar disorder; major depression; prefrontal cortex; temporal cortex; hippocampal formation; cognition
资金
- Academy of Finland
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. 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. 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, subiculum, 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. 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.
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