The histamine system in human brain. Changes in neurological and psychiatric disorders

Autoradiographical examination of the distribution of H1- and H3- histamine receptor subtypes, using [3H]-mepyramine and [3H]-R-(α) methylhistamine respectively, found high H1-receptor binding densities in neocortex, dentate gyrus and basolateral amygdala, with low binding in all subdivisions of the thalamus and other subcortical areas. H3-receptor binding was enriched within the nucleus accumbens, globus pallidus and substantia nigra, whilst was low in the hippocampus, subthalamic nucleus, temporal cortex, motor and somatosensory thalamic areas and basolateral amygdala. In situ hybridisation found H2-receptor mRNA located in the striatum, thalamus, hippocampal pyramidal cell layer and dentate gyrus, and specific laminae of neocortex. Comparison of autoradiographically determined H1-, H2- and H3-receptor binding densities between normal and pathological cases found significantly decreased (p < 0.005, ANOVA) striatal and pallidal H3-receptor binding in Huntington's disease (HD), with unaltered binding in the insular cortex. A significant correlation (p < 0.01) was present between binding in the internal globus pallidus and HD grade. Binding to the striatal H1-receptor was increased (p < 0.05, ANOVA) in Parkinson's disease (PD), whilst H2- (measured using [125I]-iodoaminopotentidine) and H3-receptor binding densities were normal in all areas examined. H1-receptor binding was also increased in the hippocampus of Lewy-body dementia (DLB) cases (p < 0.05, Students two-tailed T-Test), whilst hippocampal and cortical H2-receptor binding densities were decreased in DLB, together with Alzheimer's disease (AD) (p < 0.05, ANOVA). H3-receptor binding was increased in the insular cortex and decreased in the temporal cortex of DLB, but not AD, cases (p < 0.05, ANOVA). H1-receptor binding to tissue from patients with schizophrenia was significantly reduced in all cortical (p < 0.05, Students two-tailed T-Test), but no subcortical, areas examined. H2-receptor binding was unaltered in all areas, however H3-receptor binding was increased in the posterior putamen (p < 0.05), and highly significantly decreased (p < 0.005, Students two-tailed T-Test) in the external globus pallidus in schizophrenia. (author)