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Evidence for a central 5‐hydroxytryptamine receptor stimulation by lysergic acid diethylamide

N.‐e. Andén, H. Corrodi, Kjell Fuxé, Tomas Hökfelt

British Journal of Pharmacology September 1, 1968 DOI: 10.1111/j.1476-5381.1968.tb07943.x (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Rats
Interventions Lysergic acid diethylamide (LSD) methysergide
Topics LSD Serotonin
Keywords Stimulation 5-HT Receptor 5-hydroxytryptophan Hallucinogen Dopamine Pharmacology Spinal cord Endocrinology Tryptophan hydroxylase Central nervous system
Citations 274
Key findings LSD stimulates central serotonin receptors and reduces serotonin turnover in rat brain and spinal cord, likely through negative feedback mechanisms.

Abstract

Lysergic acid diethylamide (LSD) and the 5‐hydroxytryptamine (5‐HT) precursor, 5‐hydroxytryptophan produced similar functional effects in rat spinal cord and brain to the 5‐hydroxytryptamine precursor 5‐hydroxytryptophan, which indicates that LSD stimulates central 5‐HT receptors. By means of combined histochemical and biochemical techniques it was found that LSD reduced the turnover rate of brain and spinal cord 5‐HT, studied after inhibition of the tryptophan hydroxylase by α‐propyldopacet‐amide. The turnover of brain noradrenaline but not dopamine was somewhat accelerated. The functional and chemical effects by LSD were related to dose and to time. They were not observed after the LSD analogues 2‐bromo‐LSD and methysergide. The retardation of the 5‐HT turnover by LSD may be due to negative feed‐back mechanisms evoked by direct stimulation of the central 5‐HT receptors.

Comparable studies

Other preclinical and animal studies on LSD, most cited first.

Study Year Design Participants
Transcriptome Fingerprints Distinguish Hallucinogenic and Nonhallucinogenic 5-Hydroxytryptamine 2A Receptor Agonist Effects in Mouse Somatosensory Cortex Human embryonic kidney 293 cells stably expressing 5-HT2ARs; wild-type and 5-HT2AR... 2003 Experimental study
Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats 2020 Preclinical study
Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission Male mice 2021 Multidisciplinary experimental study with in vivo electrophysiology, optogenetics, behavioral paradigms, molecular biology, and conditional knockout mice
A non-hallucinogenic LSD analog with therapeutic potential for mood disorders. Mice and cultured rat cortical neurons 2023 Preclinical study
Lysergic Acid Diethylamide- and Mescaline-Induced Attenuation of the Effect of Punishment in the Rat Rats 1976 Experimental study

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