A detailed mapping of hist amine H 1-receptors in guinea-pig central nervous system established by autoradiography with [ 125I]iodobolpyramine

Abstract

[ 125I]Iodobolpyramine, a potent and selective histamine H 1-receptor antagonist derived from mepyramine, was used to generate light microscopic autoradiograms on sections of guinea-pig brain and spinal cord. Histamine H 1-receptors were labelled with high sensitivity over a low background as determined using mianserin or other H 1-receptor antagonists as competing agents. An atlas of H 1-receptors was established using five sagittal sections and 39 frontal sections, the latter serially prepared at 50 μm intervals. Labelled areas were identified by comparison with corresponding, classically stained sections and their density was rated according to an arbitrary scale. Autoradiographic grains were detected in a large variety of gray matter areas whereas they were generally absent from white matter areas. In the cerebral cortex, H 1-receptors are present in all areas and layers with a higher density in lamina IV. In the hippocampal formation, H 1-receptors display a laminated pattern of distribution and are the most abundant in the dentate gyrus (hilus and molecular layer) and in several areas of the subiculum and commissural complex. In the amygdaloid complex, the highest densities are found in the medial group of nuclei. In the basal forebrain, the striatum is moderately labelled whereas the nucleus accumbens, islands of Calleja and most septal nuclei are highly labelled. In the thalamus, H 1-receptors are present in high density, particularly in the anterior, median and lateral groups of nuclei. In the hypothalamus the labelling is highly heterogeneous with high densities in, for example, medial preoptic area, dorsomedial, ventromedial and most posterior nuclei, including the tuberomammillary complex in which histaminergic perikarya and short axons are present. In the cerebellum, the molecular layer is densely labelled but H 1-receptors are also detectable in the granular layer and inner nuclei. In mesencephalon and lower brainstem, H 1-receptors are particularly abundant in the nuclei of origin of most cranial nerves, in areas containing the perikarya of the catecholamine and serotonin systems and in various areas associated with vegetative reflexes, e.g. the area postrema. In the spinal cord, the highest density is found in the external layers of the dorsal horn. This highly heterogeneous distribution of H 1-receptors is discussed in the light of known distributions of histaminergic axons, other classes of histamine receptors and responses to local applications of histamine within the CNS.