Serotonin and substance P co-exist in dorsal raphe neurons of the human brain

A substance P antagonist has recently been reported to have clinical effica cy in the treatment of depression. We have therefore analysed sections from human pens, including the raphe region, with double in situ hybridization using riboprobes complementary to substance P and the 5-hydroxytryptamine t ransporter (5-HT-T mRNAs). A distinct overlap of cell bodies expressing the se two markers was observed in the dorsal and median raphe nuclei. Analysis of double-labelled sections revealed that almost half of the 5-HT neurons in the dorsal raphe and around 25% in the median raphe nucleus expressed su bstance P mRNA. The highest percentage was observed in the ventrolateral do rsal raphe nucleus and the lowest in the caudal raphe nucleus. These result s demonstrate that the phenotype of the raphe 5-HT neurons varies between s pecies, since so far no 3-HT-substance P co-existence has been demonstrated in the dorsal raphe complex of rat. The question is raised whether the pre sent results may be of significance for understanding a possible role of su bstance P in depression. (C) 1999 Lippincott Williams & Wilkins.