title: Distribution of serotonin receptor of type 6 (5-HT₆) in human brain post-mortem. A pharmacology, autoradiography and immunohistochemistry study.
abstract: The aim of this study was to investigate the distribution of serotonin (5-HT) receptors of type 6 (5-HT(6)) in postmortem human prefrontal cortex, striatum and hippocampus. The brain samples were obtained from 6 subjects who had died for causes not involving primarily or secondarily the CNS. The 5-HT(6) receptor distribution was explored by the [(125)I]SB-258585 binding to brain membranes followed by the pharmacological characterization, where possible, and by autoradiographic, immunohistochemical and immunofluorescence evaluations. A specific and saturable [(125)I]SB-258585 binding was detected in striatum only, with a pharmacological characterization consistent with that of a 5-HT(6) receptor. The autoradiography showed the presence of a specific [(125)I]SB-258585 binding distributed homogeneously in caudate, putamen and accumbens. The immunohistochemistry, carried out in the striatum only, coupled with the immunofluorescence with glial fibrillary acidic protein (GFAP) and parvalbumin (PV) showed the co-localization of 5-HT(6) receptor with PV, while indicating that this receptor subtype was expressed in neurons and not in astrocytes. Taken together, the present findings showed the presence of a higher density of 5-HT(6) receptors, as labeled by [(125)I]SB-258585, in striatum than in hippocampus and prefrontal cortex, and specifically within the neuronal body. In addition, they would suggest that striatum is one of the major potential CNS targets linked to 5-HT(6) receptor modulation.
authors.affiliation: Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, via Roma, 67, 56100 Pisa, Italy. dmarazzi@psico.med.unipi.it
authors.forename: Donatella
authors.initials: D
authors.lastname: Marazziti
authors.forename: Stefano
authors.initials: S
authors.lastname: Baroni
authors.forename: Andrea
authors.initials: A
authors.lastname: Pirone
authors.forename: Gino
authors.initials: G
authors.lastname: Giannaccini
authors.forename: Laura
authors.initials: L
authors.lastname: Betti
authors.forename: Lara
authors.initials: L
authors.lastname: Schmid
authors.forename: Elena
authors.initials: E
authors.lastname: Vatteroni
authors.forename: Lionella
authors.initials: L
authors.lastname: Palego
authors.forename: Franco
authors.initials: F
authors.lastname: Borsini
authors.forename: Fabio
authors.initials: F
authors.lastname: Bordi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Piano
authors.forename: Claudia
authors.initials: C
authors.lastname: Gargini
authors.forename: Maura
authors.initials: M
authors.lastname: Castagna
authors.forename: Mario
authors.initials: M
authors.lastname: Catena-Dell'osso
authors.forename: Antonio
authors.initials: A
authors.lastname: Lucacchini
mesh_terms: D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes / Q000378:metabolism; D010879:Piperazines / Q000378:metabolism; D011180:Postmortem Changes; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000378:metabolism*; D013449:Sulfonamides / Q000378:metabolism
chemical_list: D007457:Iodine Radioisotopes; D010879:Piperazines; D011985:Receptors, Serotonin; C418570:SB 258585; D013449:Sulfonamides; C097216:serotonin 6 receptor