A detailed autoradiographic mapping of histamine H3 receptors in rat brain areas.
[3H](R)alpha-methylhistamine, a selective histamine H3-receptor ligand, was used to perform binding studies with membranes and generate light microscopic autoradiograms in sections of the rat brain. High densities of H3 receptors were found in membranes from the anterior part of the cerebral cortex, the accumbens nucleus, the striatum, the olfactory tubercles and the substantia nigra. Autoradiography of sagittal and frontal sections evidenced specific labelling in a number of gray matter areas over a very low background, as determined using thioperamide, a selective H3-receptor antagonist, as competing drug. Labelled areas were identified by comparison with adjacent Nissl-stained sections and their labelling was rated visually. H3 receptors are heterogeneously distributed among areas known to receive histaminergic projections. In the cerebral cortex, H3 receptors are present in all areas and layers, with a rostrocaudal gradient and a higher density in deep layers (laminae IV-VI). In the hippocampal formation, H3 receptors are the most abundant in the dentate gyrus and the subiculum. In the amygdaloid complex, the highest densities are found in the central, lateral and basolateral groups of nuclei. In the basal forebrain, the accumbens nucleus, the striatum, the olfactory tubercles and the globus pallidus are highly labelled. In the thalamus in which histaminergic fibres are scarce, H3 receptors are present in a rather high density, particularly in the midline, median and intralaminar groups of nuclei. In the hypothalamus, where the densest network of histaminergic fibres is found, H3 receptors occur in moderate density, being slightly more abundant in the anterior and medial part. They are also present at the level of the tuberomammillary nuclei where they may reside on histaminergic perikarya. In mesencephalon and lower brainstem, H3 receptors are abundant in the reticular part of the substantia nigra and central gray. They are present in low density in areas of noradrenergic and serotoninergic perikarya and in the spinal cord, where a faint specific labelling is detected in the gray matter, particularly in the external layers of the dorsal horn. In the cerebellum and pituitary gland, H3 receptors are scarce. Kainic acid infusions into the striatum were followed by marked local decreases in H3 receptors evidenced in both membrane binding and autoradiographic studies. Unilateral interruption of the ascending histaminergic pathways via electrocoagulation of the lateral hypothalamic area was followed by ipsilateral increase in striatal [3H](R)alpha-methylhistamine binding, a process consistent with denervation up regulation of postsynaptic H3 receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
Unité de Neurobiologie et Pharmacologie, (U. 109) de l'INSERM, Centre Paul Broca, Paris, France.
H
H
Pollard
J
J
Moreau
J M
JM
Arrang
J C
JC
Schwartz
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology*; D001931:Brain Mapping; D017442:Histamine Agonists / Q000378:metabolism; D006640:Histidine Decarboxylase / Q000378:metabolism; D007026:Hypothalamic Area, Lateral / Q000033:anatomy & histology / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008474:Medial Forebrain Bundle / Q000033:anatomy & histology / Q000201:enzymology / Q000378:metabolism; D008761:Methylhistamines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011968:Receptors, Histamine / Q000378:metabolism*; D018100:Receptors, Histamine H3
D017442:Histamine Agonists; D008761:Methylhistamines; D011968:Receptors, Histamine; D018100:Receptors, Histamine H3; C069357:alpha-methylhistamine; D006640:Histidine Decarboxylase; D007608:Kainic Acid