Gaddum and LSD: the birth and growth of experimental and clinical neuropharmacology research on 5-HT in the UK.
The vasoconstrictor substance named serotonin was identified as 5-hydroxytryptamine (5-HT) by Maurice Rapport in 1949. In 1951, Rapport gave Gaddum samples of 5-HT substance allowing him to develop a bioassay to both detect and measure the amine. Gaddum and colleagues rapidly identified 5-HT in brain and showed that lysergic acid diethylamide (LSD) antagonized its action in peripheral tissues. Gaddum accordingly postulated that 5-HT might have a role in mood regulation. This review examines the role of UK scientists in the first 20 years following these major discoveries, discussing their role in developing assays for 5-HT in the CNS, identifying the enzymes involved in the synthesis and metabolism of 5-HT and investigating the effect of drugs on brain 5-HT. It reviews studies on the effects of LSD in humans, including Gaddum's self-administration experiments. It outlines investigations on the role of 5-HT in psychiatric disorders, including studies on the effect of antidepressant drugs on the 5-HT concentration in rodent and human brain, and the attempts to examine 5-HT biochemistry in the brains of patients with depressive illness. It is clear that a rather small group of both preclinical scientists and psychiatrists in the UK made major advances in our understanding of the role of 5-HT in the brain, paving the way for much of the knowledge now taken for granted when discussing ways that 5-HT might be involved in the control of mood and the idea that therapeutic drugs used to alleviate psychiatric illness might alter the function of cerebral 5-HT.
Institute of Neuroscience, School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK. richard.green@nottingham.ac.uk
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D000818:Animals; D006213:Hallucinogens / Q000266:history / Q000494:pharmacology*; D049673:History, 20th Century; D006801:Humans; D008238:Lysergic Acid Diethylamide / Q000266:history / Q000494:pharmacology*; D001523:Mental Disorders / Q000188:drug therapy / Q000503:physiopathology; D009480:Neuropharmacology / Q000266:history / Q000379:methods; D012107:Research Design; D012701:Serotonin / Q000266:history / Q000378:metabolism* / Q000494:pharmacology; D018490:Serotonin Agents / Q000266:history / Q000378:metabolism / Q000494:pharmacology; D006113:United Kingdom
D006213:Hallucinogens; D018490:Serotonin Agents; D012701:Serotonin; D008238:Lysergic Acid Diethylamide