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Antagonism of 5‐hydroxytryptamine by LSD 25 in the central nervous system: a possible neuronal basis for the actions of LSD 25

R.j. Boakes, Philip Bradley, Ian Briggs, A. Dray

British Journal of Pharmacology October 1, 1970 DOI: 10.1111/j.1476-5381.1970.tb09914.x (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Single neurones in the brain stem of decerebrate cats
Intervention methysergide maleate (UML 491)
Topics LSD Serotonin
Keywords Psychotomimetic Glutamate receptor Antagonism Methysergide Inhibitory postsynaptic potential Pharmacology Acetylcholine
Citations 164
Key findings LSD antagonizes both serotonin and glutamate excitation on brain stem neurons that respond to serotonin, suggesting a shared mechanism for its psychotomimetic action.

Abstract

Summary 5‐Hydroxytryptamine (5‐HT), acetylcholine (ACh), noradrenaline (NA), glutamate, d , l ‐homocysteic acid (DLH), glycine and γ‐aminobutyric acid (GABA) were applied to single neurones in the brain stem of decerebrate cats by microiontophoresis. The abilities of d ‐lysergic acid diethylamide tartrate (LSD 25), methysergide maleate (UML 491) and 2‐bromo‐lysergic acid diethylamide (BOL 148) to antagonize the actions of these compounds were studied. LSD 25 antagonized 5‐HT excitation of single neurones when applied iontophoretically or administered intravenously. LSD 25 also antagonized glutamate excitation of neurones which could be excited by 5‐HT. Inhibitory effects of 5‐HT, the action of glutamate on neurones which could be inhibited by 5‐HT and the actions of all the other compounds tested were unaffected by LSD 25. Iontophoretically applied UML 491 was also a specific antagonist to 5‐HT and glutamate excitation but was less potent than LSD 25, and BOL 148 rarely exhibited antagonism. It is suggested that antagonism to 5‐HT and glutamate excitation of brain stem neurones may be the basis of the psychotomimetic action of LSD 25. It is also suggested that there may be similarities in the mechanisms by which 5‐HT and glutamate produce excitation where they act on the same neurone.

Comparable studies

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Study Year Design Participants
Neural correlates of the LSD experience revealed by multimodal neuroimaging. Human participants 2016 Experimental study
Crystal structure of an LSD-bound human serotonin receptor 2017 Experimental study with structural biology and molecular dynamics simulations
Lysergic Acid Diethylamide: Sensitive Neuronal Units in the Midbrain Raphe Midbrain neurons containing serotonin 1968 Experimental study
Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD. Human brain 2017 Experimental study
LSD-Assisted Psychotherapy in Patients with Terminal Cancer Cancer patients 1973 Experimental study n = 60

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