Decreased serotonin content of embryonic raphe neurons following maternal administration of p-chlorophenylalanine: a quantitative immunocytochemical study.

Previous studies from this laboratory have suggested that serotonergic (5-HT) neurons may influence the differentiation of their embryonic target cells in the developing rat brain. The present study was designed to determine whether or not maternal p-chlorophenylalanine (pCPA) administration could deplete serotonin (5-HT) in developing 5-HT neurons during embryonic days 13-15, when the effects of pCPA on neuronal genesis have been observed previously. For this study, pCPA was administered to timed-pregnant rats and embryos were sacrificed at two different gestational ages, embryonic days 13-14 (E13-14) and 14-15 (E14-15). Immunotitration experiments were carried out on tissue sections, using an antiserum to 5-HT-hemocyanin conjugates to obtain a relative estimate of the amount of 5-HT contained within individual 5-HT neurons of embryos from pCPA-treated and control mothers. Diminished immunoreactivity as a consequence of addition of increasing amounts of antigen was then quantitated on a relative scale by comparison with the amount of immunoreactivity present when no antigen was added to the primary antiserum. Two major findings resulted from this study: maternal pCPA treatment depleted 5-HT by approximately 50% in developing 5-HT neurons at embryonic ages E13-14 and E14-15, but depletion appeared to be greatest in the youngest embryos; developing 5-HT neurons increased their content of neurotransmitter by approximately 10-fold during this one day of embryonic development, an effect which could be observed in both pCPA-treated and control animals.(ABSTRACT TRUNCATED AT 250 WORDS)