Quantitative morphometric analysis of two types of serotonin-immunoreactive nerve fibres differentially responding to p-chlorophenylalanine treatment in the rat brain.

Two types of serotonin neurons differentially responding to treatment with p-chlorophenylalanine, a potent inhibitor of serotonin synthesis, have been demonstrated in the rat brain by immunohistochemistry using a serotonin monoclonal antibody in combination with a quantitative morphometric analysis. In control rats, the numerical density of serotonin-immunoreactive varicosities and terminals varied considerably from region to region. In p-chlorophenylalanine-treated rats, the numerical density was reduced in every region, but the degree of reduction in each region differed markedly. No correlation was seen in values of the numerical density between the control and p-chlorophenylalanine-treated rats, indicating that serotonin-positive axons in p-chlorophenylalanine-treated rats were present independent of the degrees of the axon density seen in the controls. It is postulated, therefore, that there are at least two types of positive axons; one highly sensitive to p-chlorophenylalanine treatment and another relatively resistant to it. Since the numerical density in any region was always smaller in p-chlorophenylalanine-treated rats than in the controls, p-chlorophenylalanine-sensitive axons appeared to be more or less distributed in every region where positive axons were detectable under normal conditions. However, a number of regions were innervated purely by p-chlorophenylalanine-sensitive axons. By contrast, p-chlorophenylalanine-insensitive axons were observed in several definite regions. These regions appeared to be related to the limbic system, or cranial motor and parasympathetic nuclei. In the latter nuclei, p-chlorophenylalanine-insensitive axons seemed to possess such common morphological features as having relatively large varicosities and being situated adjacent to neural somata, suggesting their inhibitory roles in neurotransmission. The present result indicates that the two types of serotonin axons may play important roles in the behavioural events observed in rats following p-chlorophenylalanine treatment.