title: Serotonergic neurotransmission in the living human brain: a positron emission tomography study using [¹¹C]dasb and [¹¹C]WAY100635 in young healthy men.
abstract: The central serotonergic (5-HT) system is closely involved in regulating various mental functions such as mood and emotion. In this system, the serotonin transporter (5-HTT) and the 5-HT(1A) receptor play important roles in the pathophysiology and treatment of mood and anxiety disorders. However, only a few integrated databases have considered the intraindividual relationship between pre- and postsynaptic serotonergic transmission. In the present study, we constructed a database of 5-HTT and 5-HT(1A) receptors using positron emission tomography (PET) with [¹¹C]DASB and [¹¹C]WAY100635, respectively. Seventeen healthy young men participated in this study. After anatomic standardization of original images, BP(ND) was calculated on a voxel-by-voxel basis using reference tissue methods. The highest binding to 5-HTT was observed in the dorsal raphe nucleus, striatum, and thalamus; moderate binding, in the insula and cingulate cortex; and very low binding, in the cerebral neocortex. In contrast, the highest binding to 5-HT(1A) receptors was seen in the hippocampal regions, insula, neocortical regions, and dorsal raphe nucleus, and very low binding was found in the thalamus and basal ganglia. These distribution patterns were in agreement with those reported in human postmortem studies and previous PET investigations. In addition, exploratory analysis indicated significant negative correlations between the BP(ND) values with both radiotracers in certain regions of the brain, such as the cingulate, insula, and frontal, temporal and parietal cortices (Pearson's correlation, P < 0.05). These databases facilitate the understanding of the regional distribution of serotonergic neurotransmission function in the living human brain and the pathophysiology of various neuropsychiatric disorders.
authors.affiliation: Department of Molecular Neuroimaging, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan. hrtakano@nirs.go.jp
authors.forename: Harumasa
authors.initials: H
authors.lastname: Takano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Takahashi
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Arakawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Okumura
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Kodaka
authors.forename: Tatsui
authors.initials: T
authors.lastname: Otsuka
authors.forename: Motoichiro
authors.initials: M
authors.lastname: Kato
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
mesh_terms: D000328:Adult; D001596:Benzylamines; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D010879:Piperazines; D049268:Positron-Emission Tomography; D011725:Pyridines; D019275:Radiopharmaceuticals; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D055815:Young Adult
chemical_list: D001596:Benzylamines; D002250:Carbon Radioisotopes; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; D010879:Piperazines; D011725:Pyridines; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide