Effects of lysergic acid diethylamide on the metabolism of brain 5-hydroxytryptamine

The effects of d-lysergic acid diethylamide (LSD), in doses ranging from 200 to 1300 μg/kg, on the time course of the changes in brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic add (5-HIAA) have been studied in male Sprague-Dawley rats. The results show that LSD influences 5-HT metabolism in brain in a complex way. After i.v. administration of 200 μg/kg LSD, brain 5-HT increases to a maximum of 15–20 per cent at 25 min, while 5-HIAA decreases 15–20 per cent at 20 min. After i.p. administration, which prolongs the total period during which LSD is found in the brain, the time course is spread out and is triphasic: (1) in the first 30 min after 520 or 1300 μg/kg, brain 5-HT increases 15–20 per cent and brain 5-HIAA decreases 15–20 per cent; (2) from 30 to 60 min, 5-HT still increases, while the 5-HIAA level is returning to normal; (3) after 60 min, both 5-HT and 5-HIAA levels decrease at a parallel rate.Both differential and density gradient centrifugation show that 5-HIAA is not present in any particulate fraction, but 5-HT is localized in both the Whittaker B (nerve-ending particle) and the microsomal fractions. Thirty min after 520 μg/kg LSD i.p., the 5-HT content in both fractions is increased 25–30 per cent.These results are consistent with increased binding of 5-HT or an effect of LSD on control mechanisms that regulate 5-HT turnover in the rat brain, or both.