Effects of intraventricuear p-chloroamphetamine and its analogues on cerebral 5-HT
A. Shermana, E. M. Gála, R. W. Fuller* and B. B. Molloy*
a Neurochemical Research Laboratory, Department of Psychiatry, University of Iowa College of Medicine, Iowa City, Iowa, USA
* The Lilly Research Laboratories, Eli Lilly and Company., Indianapolis, Indiana, USA
Accepted 26 March 1975. Available online 6 November 2002.
A dose-response curve for serotonin (5-HT) depletion by intraventricularly administered p-chloroamphetamine was established along with its effect on the activity of tryptophan-5-hydroxylase. The effects of several analogues on cerebral 5-HT were assessed following their intraventricular administration. Changes in 5-HT were determined at various time intervals after administration of the analogues. The minimal intraventricular dose at which p-chloroamphetamine depressed 5-HT at six hr after injection was 200μg. Of the agents tested, only chloroamphetamine reduced both 5-HT and 5-hydroxyindoleacetic acid at six hours. p-Fluoroamphetamine and fenfluramine, like p-chloroamphetamine, produced a long-lasting depression of cerebral 5-HT levels. Intraventricularly injected p-chloroamphetamine reduced activity of tryptophan-5-hydroxylase with and without iprindole pretreatment, but had little effect on catecholamine levels. The results are compatible with the previous hypothesis that p-chloroamphetamine is converted to some metabolite responsible for the long-term neurotoxic effects.