Serotonin-containing neuronal perikarya and terminals: differential effects of p-chlorophenylalanine

Abstract

Previous studies have shown that p-cholorophenylalanine (PCPA), an irreversible inhibitor of serotonin (5-HT) synthesis at the tryptophan hydroxylase step, fails to prevent the l-tryptophan-induced increase in the fluorescence of 5-HT-containing neuronal perikarya of the brain stem raphe nuclei, although there is a marked depletion in whole brain 5-HT concentration. In an effort to explain this apparent discrepancy, the effect of PCPA upon the histofluorescence of raphe cell terminals in the midbrain and forebrain of rats was examined. Demonstration of the fluorescence of raphe cell terminals was aided in part by pretreatment with l-tryptophan in the presence of a monoamine oxidase inhibitor. PCPA was found to produce a marked decrease in the fluorescence of raphe terminals but, in agreement with previous results, not in the perikarya. Parallel biochemical studies showed that 5-HT was depleted by PCPA (with or without l-tryptophan loading) to a much greater extent in the forebrain (a region rich in raphe terminals), than in a block of tissue containing the raphe cell perikarya. These results indicate that the synthesis of 5-HT is more susceptible to inhibition by PCPA in the terminals than in the perikarya of raphe neurons, perhaps due to a continued synthesis of new tryptophan hydroxylase enzyme in the latter site.