THE DISTRIBUTION OF 5-HT1A AND 5-HT2A RECEPTOR MESSENGER-RNA IN HUMAN BRAIN

We have examined the distribution of 5-HT1A and 5-HT2A receptor mRNAs in post-mortem human hippocampus, neocortex, raphe nuclei, cerebellum and basal ganglia using in situ hybridization histochemistry. Receptor transcripts in brains from two males and two females (mean age +/- S.D. = 70 +/- 4 years; post-mortem interval = 29 +/- 6 h) were visualised with S-35-radiolabelled synthetic oligodeoxyribonucleic acid probes. In the hippocampus, 5-HT1A receptor mRNA was present in all fields, especially CA1. In the parahippocampal gyrus and neocortical regions 5-HT1A receptor mRNA was enhanced in superficial and middle laminae. 5-HT1A receptor mRNA was particularly abundant in the raphe and other serotonergic cell groups of the brainstem. The analysis of emulsion dipped sections showed 5-HT1A receptor mRNA to be concentrated in pyramidal neurons, together with the granule cells of the dentate gyrus. In neocortical areas lamina III pyramidal neurons were more heavily labelled than those in lamina V. There was no evidence of glial expression of 5-HT1A receptor mRNA in grey matter or white matter compartments. 5-HT2A receptor mRNA was present in all neocortical areas examined, where it was located in pyramidal neurons, of lamina V more than in those of lamina III, as well as in putative interneurons, especially within lamina IVc of the striate cortex. 5-HT2A receptor mRNA was observed at minimal levels in the hippocampus and not in the raphe. Neither 5-HT1A nor 5-HT2A receptor mRNA were detected in the cerebellum, substantia nigra or striatum. The ability to detect these transcripts at the regional and cellular level will help reveal important details of the 5-HT receptor system in the human brain. This includes the investigation of their putative roles in the normal chemoarchitecture and in pathophysiological brain processes.