title: Antipsychotic binding to the dopamine-3 receptor in humans: A PET study with [(11)C]-(+)-PHNO.
abstract: BACKGROUND
  All currently available antipsychotic medications bind to both the dopamine-2 (D2) and dopamine-3 (D3) receptors in vitro. However, there is conflicting evidence from in vivo studies about whether or not antipsychotic medications bind to the D3 receptor (D3R). The purpose of this study was to determine whether acute doses of risperidone bind to the D3R in humans.
  
  
  METHODS
  We performed PET scans on an mCT scanner with [(11)C]-(+)-PHNO injected as a bolus, before and after a 2mg oral dose of risperidone in five medication free subjects with schizophrenia. The subjects were scanned for 120min and underwent an MRI scan for region of interest delineation and coregistration. Cerebellum was used as a reference region. Simplified reference tissue modeling (SRTM) was used to calculate BPND.
  
  
  RESULTS
  We observed binding to the D3R receptor by risperidone as evidenced by observable occupancy in regions in which the [(11)C]-(+)-PHNO signal is almost exclusively from the D3R (i.e., substantia nigra/ventral tegmental area). Using a regression model to estimate D2R:D3R selectivity, we observed a D2R:D3R selectivity of 2.1 for risperidone.
  
  
  CONCLUSIONS
  Our preliminary results provide further support that acute doses of antipsychotic medications bind to the D3R and provide additional support for the further development of this receptor as a treatment target in schizophrenia.
authors.affiliation: Columbia University, Department of Psychiatry, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA. Electronic address: ragygir@nyspi.columbia.edu.
authors.forename: Ragy R
authors.initials: RR
authors.lastname: Girgis
authors.affiliation: Columbia University, Department of Psychiatry, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Columbia University, Department of Psychiatry, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Roberto B
authors.initials: RB
authors.lastname: Gil
authors.affiliation: Columbia University, Department of Psychiatry, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hackett
authors.affiliation: Columbia University, Department of Psychiatry, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Najate
authors.initials: N
authors.lastname: Ojeil
authors.affiliation: Columbia University, Department of Psychiatry, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.affiliation: Columbia University, Department of Psychiatry, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Slifstein
authors.affiliation: Columbia University, Department of Psychiatry, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Anissa
authors.initials: A
authors.lastname: Abi-Dargham
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects*; D001931:Brain Mapping; D018491:Dopamine Agonists / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D011569:Psychiatric Status Rating Scales; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D018491:Dopamine Agonists; D010078:Oxazines; D050637:Receptors, Dopamine D3; C042631:naxagolide
keywords: Dopamine-3; Occupancy; PET; PHNO; Risperidone; Schizophrenia