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CC/NUMBER 16 APRIL 16, 1984 This Week’s Citation Classic™ Vogt M. The concentration of sympathin in different parts of the central nervous system under normal conditions and after the administration of drugs. J. Physiology 123:451-81, 1954. [Department of Pharmacology, University of Edinburgh, Scotland] A map of the distribution of noradrenaline (NA) and adrenaline was obtained by bioassay of extracts of about 50 freshly dissected regions of the dog’s brain and spinal cord. The NA concentration ranged from 2.0 to 0.01 µg/g fresh tissue. [The SCI ® indicates that this paper has been cited in over 995 publications since 1955.] cerebellar cortex showed that the NA was so much greater in hypothalamus than in cerebellar cortex (both highly vascularized regions) that the explanation of the difference by variable vascularity could not be correct. This observation led to my undertaking a survey of concentrations of NA and adrenaline in many brain regions with a method which used paper chromatography followed by Marthe Vogt Institute of Animal Physiology Agricultural Research Council Babraham, Cambridge CB2 4AT England biological assay, at the time the most sensitive method available. The results could hardly be explained by assuming that vasomotor nerves were the main source of cerebral NA, and March 15, 1984 suggested a characteristic uneven distribution of noradrenergic neurones in the brain tissue “The work was done in J.H. Gaddum’s itself. Fluorescence microscopy carried out laboratory at the University of Edinburgh. It soon afterward by Swedish workers showed took about four years to carry out (1950-1953), that catecholamine fluorescence was indeed but the manuscript was accidentally buried on present within neurones, many of which were the editor’s desk until I finally had the courage found in the hypothalamus, but only a few in to enquire about its fate. It was then published the cerebellum. with great speed and without editorial corrections. “Since dopamine (DA) is an obligatory precursor of NA and adrenaline, it is found in all “The fact that cholinergic neurones (identified catecholamine containing neurons. However, by the presence of choline acetyltransferase) as shown by Carlsson,2 there are large brain had been shown 1 to be very unevenly regions in which DA is the final product, and distributed in the brain and practically absent where it is therefore supposed to play the role from of a transmitter or ‘modulator’ of impulses. large regions suggested that acetylcholine could not be the only nervous Three transmitter in the central nervous system. The pathways, the arcuate nucleus, and certain only other transmitter known at that time (1952) layers in some cortical areas. There is in peripheral nerves was noradrenaline (NA). A particular interest in this last site, since the small amount of this transmitter was known to clinically beneficial effect of antagonists of DA occur in the brain but was assumed to be (such as chlorpromazine) in schizophrenia can localized exclusively in nerves to the blood hardly be expected to be due to their action on vessels. the nigro-striatal system or on the arcuate “A preliminary comparison of the concentration of NA in hypothalamus and examples are the nigro-striatal nucleus, but a site of action in the cerebral cortex is a clear possibility.” 1. Feldberg W & Vogt M. Acetylcholine synthesis in different regions of the central nervous system. J. Physiology 107:372-81, 1948. (Cited 265 times since 1955.) 2. Carisson A. The occurrence, distribution and physiological role of catecholamines in the nervous system. Pharmacol Rev. 11:490-3, 1959 (Cited 380 times.) 227