title: Lack of association between the serotonin transporter and serotonin 1A receptor: an in vivo PET imaging study in healthy adults.
abstract: The serotonin neurotransmitter system is modulated in part by the uptake of synaptically released serotonin (5-HT) by the serotonin transporter (5-HTT), and by specific serotonin autoreceptors such as the somatodendritic 5-HT1A receptor, which can limit serotonin neuron depolarization. However, little is known about how 5-HTT and 5-HT1A are related in vivo. To study this question, we reanalyzed positron emission tomography (PET) data obtained earlier in 40 healthy participants (21 females) using [(11)C]WAY-100635 for quantification of 5-HT1A binding and [(11)C](+)-McN-5652 for quantification of 5-HTT binding. We hypothesized negative correlations between 5-HT1A binding in the raphe nuclei (RN) and 5-HTT binding in RN terminal field regions. Controlling for sex, no significant correlations were found (all p>0.05). Similarly, an exploratory analysis correlating whole-brain voxel-wise 5-HTT binding with 5-HT1A binding in RN identified no significant clusters meeting our a priori statistical threshold. The lack of correlation between 5-HT1A and 5-HTT binding observed in the current study may be due to the different temporal responsiveness of regulatory processes controlling the somatodendritic 5-HT1A receptor and 5-HTT in response to changing availability of intrasynaptic serotonin.
authors: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 1051 Riverside Drive #42, New York, NY 10032, USA.
authors: Michael
authors: M
authors: Strupp-Levitsky
authors: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 1051 Riverside Drive #42, New York, NY 10032, USA; Department of Psychiatry, Columbia University, 1051 Riverside Drive #42, New York, NY 10032, USA. Electronic address: jm2233@cumc.columbia.edu.
authors: Jeffrey M
authors: JM
authors: Miller
authors: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 1051 Riverside Drive #42, New York, NY 10032, USA; Department of Psychiatry, Columbia University, 1051 Riverside Drive #42, New York, NY 10032, USA.
authors: Harry
authors: H
authors: Rubin-Falcone
authors: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 1051 Riverside Drive #42, New York, NY 10032, USA; Department of Psychiatry, Columbia University, 1051 Riverside Drive #42, New York, NY 10032, USA.
authors: Francesca
authors: F
authors: Zanderigo
authors: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 1051 Riverside Drive #42, New York, NY 10032, USA; Department of Psychiatry, Columbia University, 1051 Riverside Drive #42, New York, NY 10032, USA.
authors: Matthew S
authors: MS
authors: Milak
authors: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 1051 Riverside Drive #42, New York, NY 10032, USA; Department of Psychiatry, Columbia University, 1051 Riverside Drive #42, New York, NY 10032, USA.
authors: Gregory
authors: G
authors: Sullivan
authors: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 1051 Riverside Drive #42, New York, NY 10032, USA; Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors: R Todd
authors: RT
authors: Ogden
authors: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 1051 Riverside Drive #42, New York, NY 10032, USA; Department of Psychiatry, Columbia University, 1051 Riverside Drive #42, New York, NY 10032, USA.
authors: Maria A
authors: MA
authors: Oquendo
authors: Now at Department of Psychiatry, Department of Radiology, Stony Brook Medicine, Stony Brook, NY, USA.
authors: Christine
authors: C
authors: DeLorenzo
authors: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 1051 Riverside Drive #42, New York, NY 10032, USA; Department of Psychiatry, Columbia University, 1051 Riverside Drive #42, New York, NY 10032, USA.
authors: Norman
authors: N
authors: Simpson
authors: Now at Department of Psychiatry, Department of Radiology, Stony Brook Medicine, Stony Brook, NY, USA.
authors: Ramin V
authors: RV
authors: Parsey
authors: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 1051 Riverside Drive #42, New York, NY 10032, USA; Department of Psychiatry, Columbia University, 1051 Riverside Drive #42, New York, NY 10032, USA.
authors: J John
authors: JJ
authors: Mann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007546:Isoquinolines; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D010879:Piperazines; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines; D011903:Raphe Nuclei / Q000000981:diagnostic imaging / Q000378:metabolism*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: D007546:Isoquinolines; D010879:Piperazines; D011725:Pyridines; 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; C058079:McN 5652
keywords: PET; Serotonin; Serotonin 1A receptor; Serotonin transporter