IMMUNO-LOCALIZATION OF SEROTONIN 5-HT6 RECEPTOR-LIKE MATERIAL IN THE RAT CENTRAL-NERVOUS-SYSTEM

In order to map the recently cloned serotonin 5-HT6 receptor in the ra t brain and spinal cord, polyclonal antibodies were raised against a s ynthetic octadecapeptide corresponding to a specific portion (Leu(398) -Val(415)) of the C-terminal domain of this receptor. Antibodies were detected by enzyme-linked immunosorbent assay as soon as one month aft er the first injection to rabbits of the peptide coupled to keyhole li mpet hemocyanin. Immunoautoradiographic experiments with antibodies af finity-purified on Affi-Gel coupled to the peptide antigen showed that 5-HT6-like immunoreactive material was abundant in the olfactory tube rcle (plexiform layer), cerebral cortex (frontal and entorhinal areas) , nucleus accumbens, striatum, hippocampus (strata oriens and radiatum of the CA1 area, molecular layer of the dentate gyrus) and the molecu lar layer of the cerebellum. A specific immunolabeling, but at moderat e intensity, was also observed in the thalamus, substantia nigra, supe rficial layer of the superior colliculus, motor trigeminal nucleus and facial nucleus. In contrast, no 5-HT6-like immunoreactive material wa s found in white matter areas. As the regional distribution of 5-HT6 r eceptor-like immunoreactivity marched generally that previously found for the 5-HT6 receptor mRNA, one could infer that this receptor protei n is addressed in the vicinity of its synthesis site, i.e. on somas an d/or dendrites. Indeed, immunohistochemistry at the light and electron microscope level showed that 5-HT6-like immunoreactivity was associat ed with dendritic processes in both the striatum and the dentate gyrus of the hippocampus. The relative abundance of 5-HT6 receptor-like imm unoreactivity in extrapyramidal and limbic areas suggests that 5-HT6 r eceptors may participate in the serotoninergic control of motor functi on and mood-dependent behavior, respectively.