Gaddum and LSD: the birth and growth of experimental and clinical neuropharmacology research on 5‐HT in the UK

Serotonin (5-hydroxytryptamine or 5-HT) was identified as a vasoconstrictor substance by Maurice Rapport in 1949. Gaddum and colleagues soon detected 5-HT in brain and discovered that lysergic acid diethylamide (LSD) antagonized its action in peripheral tissues, leading Gaddum to propose that 5-HT might regulate mood. This review covers the first 20 years of UK scientists' contributions, including developing assays for brain 5-HT, identifying its synthesis and metabolism enzymes, and studying drug effects on brain 5-HT. It describes human LSD experiments, including Gaddum's self-administration, and investigations into 5-HT's role in psychiatric disorders and antidepressant drug effects on 5-HT levels in rodent and human brain.

Study at a glance

Abstract

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. British Journal of Pharmacology (2008) 154 , 1583–1599; doi: 10.1038/bjp.2008.207 ; published online 26 May 2008