title: Reductions in brain 5-HT1B receptor availability in primarily cocaine-dependent humans.
abstract: BACKGROUND
  Preclinical evidence implicates the serotonin receptor 5-hydroxytryptamine 1B (5-HT1B) in the effects of cocaine. This study explores 5-HT1B in humans by examining receptor availability in vivo in subjects whose primary addiction is cocaine dependence (CD) using positron emission tomography.
  
  
  METHODS
  Study participants included 14 medically healthy subjects with CD (mean age = 41 ± 6 years) who were compared with 14 age-matched healthy control subjects (mean age = 41 ± 8 years) with no past or current history of cocaine or other illicit substance abuse. Participants underwent magnetic resonance imaging followed by positron emission tomography with the highly selective 5-HT1B tracer, [(11)C]P943, for purposes of quantifying regional binding potential. Voxel-based morphometry and gray matter masking also were employed to control for potential partial volume effects.
  
  
  RESULTS
  The [(11)C]P943 positron emission tomography imaging data in nine candidate regions (amygdala, anterior cingulate cortex, caudate, frontal cortex, hypothalamus, pallidum, putamen, thalamus, and ventral striatum) showed significant or nearly significant reductions of regional binding potential in subjects with CD in three regions: anterior cingulate (-16%, p < .01), hypothalamus (-16%, p = .03), and frontal cortex (-7%, p = .08). Voxel-based morphometry showed significant gray matter reductions in the frontal cortex of subjects with CD. After gray matter masking, statistically significant reductions in the [(11)C]P943 regional binding potential were either retained (anterior cingulate, -14%, p = .01; hypothalamus, -20%, p < .01) or achieved (frontal cortex, -14%, p < .01). Whole-brain voxel-wise parameter estimation confirmed these results. Secondary analyses were also significant in some regions for years of cocaine and daily tobacco use.
  
  
  CONCLUSIONS
  The reductions found in this study suggest that 5-HT1B receptors may contribute to the etiology or expression of CD and potentially represent a target for medication development.
authors.affiliation: Departments of Psychiatry (DM, ZB, BPi, JC, JW, PG, MNP, RTM); Diagnostic Radiology (DM, BPl, J-DG, SN, JR, YH, REC), Yale University, New Haven. Electronic address: david.matuskey@yale.edu.
authors.forename: David
authors.initials: D
authors.lastname: Matuskey
authors.affiliation: Departments of Psychiatry (DM, ZB, BPi, JC, JW, PG, MNP, RTM); Bristol-Myers Squibb (ZB), Wallingford, Connecticut.
authors.forename: Zubin
authors.initials: Z
authors.lastname: Bhagwagar
authors.affiliation: Diagnostic Radiology (DM, BPl, J-DG, SN, JR, YH, REC), Yale University, New Haven.
authors.forename: Beata
authors.initials: B
authors.lastname: Planeta
authors.affiliation: Departments of Psychiatry (DM, ZB, BPi, JC, JW, PG, MNP, RTM).
authors.forename: Brian
authors.initials: B
authors.lastname: Pittman
authors.affiliation: Diagnostic Radiology (DM, BPl, J-DG, SN, JR, YH, REC), Yale University, New Haven.
authors.forename: Jean-Dominique
authors.initials: JD
authors.lastname: Gallezot
authors.affiliation: Departments of Psychiatry (DM, ZB, BPi, JC, JW, PG, MNP, RTM).
authors.forename: Jason
authors.initials: J
authors.lastname: Chen
authors.affiliation: Departments of Psychiatry (DM, ZB, BPi, JC, JW, PG, MNP, RTM).
authors.forename: Jane
authors.initials: J
authors.lastname: Wanyiri
authors.affiliation: Diagnostic Radiology (DM, BPl, J-DG, SN, JR, YH, REC), Yale University, New Haven.
authors.forename: Soheila
authors.initials: S
authors.lastname: Najafzadeh
authors.affiliation: Diagnostic Radiology (DM, BPl, J-DG, SN, JR, YH, REC), Yale University, New Haven.
authors.forename: Jim
authors.initials: J
authors.lastname: Ropchan
authors.affiliation: Departments of Psychiatry (DM, ZB, BPi, JC, JW, PG, MNP, RTM).
authors.forename: Paul
authors.initials: P
authors.lastname: Geha
authors.affiliation: Diagnostic Radiology (DM, BPl, J-DG, SN, JR, YH, REC), Yale University, New Haven.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Departments of Psychiatry (DM, ZB, BPi, JC, JW, PG, MNP, RTM).
authors.forename: Marc N
authors.initials: MN
authors.lastname: Potenza
authors.affiliation: Department of Psychiatry (AN), New York University School of Medicine, New York, New York.
authors.forename: Alexander
authors.initials: A
authors.lastname: Neumeister
authors.affiliation: Diagnostic Radiology (DM, BPl, J-DG, SN, JR, YH, REC), Yale University, New Haven.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.affiliation: Departments of Psychiatry (DM, ZB, BPi, JC, JW, PG, MNP, RTM).
authors.forename: Robert T
authors.initials: RT
authors.lastname: Malison
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*
chemical_list: D002250:Carbon Radioisotopes; D044302:Receptor, Serotonin, 5-HT1B
keywords: 5-HT(1B); PET; VBM; cocaine; human; serotonin