Accumulation and disappearance of 3H-5-hydroxytryptamine formed from 3H-tryptophan in mouse brain; Effect of LSD-25

3H-Tryptophan was administered intravenously to conscious mice by injection or constant rate infusion. Endogenous tryptophan and 5-hydroxytryptamine levels were not significantly altered by this treatment. 3H-5-HT formed in vivo from the labelled precursor was identified by paper chromatography. Following a pulse-injection of 3H-tryptophan the level of 3H-5-HT in brain rapidly increased reaching a peak within 30 min. Pretreatment of the animals with the tryptophan hydroxylase inhibitor, p-chlorophenylalanine or reserpine, markedly reduced the accumulation of 3H-5-HT. Following the initial peak, the content of 3H-5-HT declined over several hours at a rate that seemed to be exponential between 30 and 180 min after precursor administration with a half-life of about 60 min. Treatment with p-chloro-phenylalanine 60 min after precursor administration did not accelerate the rate of disappearance of 3H-5-HT indicating that the decline of 3H-5-HT content is predominantly determined by turnover of the amine. The procedures were used to study the effect of LSD-25 on mouse brain serotonin metabolism. Following LSD-25 treatment the rates of accumulation and disappearance of 3H-5-HT after 3H-tryptophan administration were markedly reduced. The contents of labelled tryptophan and endogenous tryptophan and 5-HT levels were not altered by drug treatment. The results indicate that LSD-25 reduces both synthesis and turnover of 5-HT in brain. The LSD-25 analogue BOL 148 showed no effect on brain 5-HT metabolism. Possible mechanisms of action of LSD-25 are discussed.