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

Lysergic acid diethylamide (LSD) produces functional effects in rat spinal cord and brain similar to those of the serotonin (5-hydroxytryptamine) precursor 5-hydroxytryptophan, indicating that LSD stimulates central serotonin receptors. Using histochemical and biochemical techniques, LSD reduced the turnover rate of serotonin in the brain and spinal cord after inhibition of tryptophan hydroxylase. The turnover of noradrenaline, but not dopamine, was somewhat accelerated. These effects were dose- and time-dependent and were not observed with the LSD analogues 2-bromo-LSD and methysergide. The retardation of serotonin turnover by LSD may result from negative feedback mechanisms triggered by direct stimulation of central serotonin receptors.

Study at a glance

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.