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Fifty years of dopamine research

Björklund, Anders and Dunnett, Stephen Bruce 2007. Fifty years of dopamine research. Trends in Neurosciences 30 (5) , pp. 185-187. 10.1016/j.tins.2007.03.004

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This year marks the 50th anniversary of the discovery of dopamine as a putative independent neurotransmitter in the nervous system. The amine 3-hydroxytyramine (‘dopamine’) had earlier been identified as an intermediary in the synthesis of noradrenaline and adrenaline from tyrosine. In 1957, Arvid Carlsson, Margit Lindqvist, Tor Magnusson and Bertil Waldeck, in Lund 1 and 2, and Kathleen Montagu, working in Hans Weil-Malherbe's laboratory at the Runwell Hospital outside London [3], made the seminal observations that would lead to the unravelling in subsequent years of the role of dopamine as a transmitter in the CNS, independent of its role as a precursor in the synthesis of noradrenaline and adrenaline. In 1957–1958, Carlsson and co-workers made the intriguing observation that the akinetic effects of reserpine could be reversed by an intravenous injection of the dopamine (and noradrenaline) precursor 3,4-dihydroxyphenylalanine (DOPA) and were correlated to a recovery of dopamine, but not noradrenaline, content in the brain, suggesting that depletion of dopamine, rather than noradrenaline or 5-hydroxytryptamine (5-HT, or serotonin), was the cause of the akinetic state in reserpine-treated animals. The following year, Carlsson's students Ǻke Bertler and Evald Rosengren [4], and Sano and collaborators in Japan [5], reported that the bulk of dopamine in the brain was located in the striatum (a structure containing little noradrenaline) 4 and 5, thus providing further support for the hypothesis that this new, putative transmitter might have a central role in the control of motor function [6]. As described by Oleh Hornykiewicz in his review of these early events [7], it was the 1959 paper of Bertler and Rosengren that stimulated him, together with Herbert Ehringer in Vienna, to embark on a series of further studies of the distribution of dopamine in human post-mortem brains, which showed that the dopamine concentration is markedly and consistently reduced in the caudate and putamen of patients with Parkinson's disease (PD) [8]. These findings led to the first trials of L-DOPA in PD patients by Walther Birkmayer and Oleh Hornykiewicz [9] in Vienna and by André Barbeau, Ted Sourkes and Gerald Murphy [10]in Montreal. The real breakthrough, however, came five years later, in 1967, when George Cotzias in New York developed the clinically efficacious, high-dose oral DOPA treatment that is still used today [11]. More detailed, personal accounts of these early discoveries are provided in reviews by Carlsson [12] and Hornykiewicz [7].

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Cell Press
ISSN: 0166-2236
Last Modified: 04 Jun 2017 06:34

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