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

1. 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.2. 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 alpha-propyldopacetamide. The turnover of brain noradrenaline but not dopamine was somewhat accelerated.3. 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 methylsergide.4. 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.