The action of fenfluramine andp-chloramphetamine on serotonergic mechanisms: A comparative study in rat brain nuclei.

A single injection of fenfluramine orp-chloroamphetamine (PCA) (100 μmol/kg intraperitoneally) decreases the serotonin (5HT) content and the tryptophan hydroxylase activity in various areas of the rat brain. Other reports have shown that a single injection of fenfluramine or PCA causes cytopathological changes in a serotonergic midbrain nucleus which was termed B9 by Dahlstrom and Fuxe (1). Despite this cytopathological change, fenfluramine fails to reduce the tryptophan hydroxylase activity in B9. In hippocampus the decrease of tryptophan hydroxylase elicited by fenfluramine persists for less than 21 days; in contrast PCA reduces the tryptophan hydroxylase activity in hippocampus, striatum, septal nuclei and B9 for longer than 21 days. Probably the decrease of tryptophan hydroxylase elicited by PCA in B9 is due to retrograde degeneration; the intensity and duration of the biochemical lesion elicited by fenfluramine and PCA in serotonergic terminals are a factor in determining the extent of the biochemical lesion in serotonergic cell bodies.