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Aghajanian GK, Haigler HJ. 
“Mode of Action of LSD on Serotonergic Neurons”. 
Advanc Bioche Psychopharacol. 1974;l0:167-177.
Much evidence has now accumulated that D-lysergic acid diethylamide (LSD) can produce profound alterations in the biochem-istry and physiology of serotonergic neurons in brain. Originally, the hypothesis that LSD might produce its effects on behavior by interacting with serotonin (5-hydroxytryptamine, 5-HT) was proposed by Gaddum (1953) and by Woolley and Shaw (1954). Specifically, they suggested that LSD might be an antagonist of 5-HT in the central nectarous system. This concept, which antedated by more than a decade the discovery and mapping of serotonergic neurons in brain (Dahlström and Fuxe, 1965), was based on some of the following observations: (1) LSD and 5-HT both contain an indolethylamine nucleus; (2) LSD could antagonize the effects of 5-HT on certain smooth muscle preparations (Gaddum, 1953; Woolley and Shaw, 1954); (3) the presence of 5-HT was found in the brain (Twarog and Page, 1953; Amin, Crawford, and Gaddum, 1954). The hypothesis that LSD acts in the brain by antagonizing 5-HT was soon challenged by the finding that 2-bromo LSD (BOL) was as potent as LSD in antagonizing 5-HT in peripheral systems, but had little behavioral effect (Cerletti and Rothlin, 1955). However, it was later determined that LSD, particularly at low concentrations, could have a 5-HT-like action in various peripheral systems (Costa, 1956; Shaw and Woolley, 1956; Welsh, 1957. Mansour, 1957). Thus it became apparent that studies with peripheral tissues could not settle the question as to the precise nature of the interaction between LSD and 5-HT in the brain itself.
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