title: Varenicline increases in vivo striatal dopamine D2/3 receptor binding: an ultra-high-resolution pinhole [123I]IBZM SPECT study in rats.
abstract: BACKGROUND
  Ex vivo storage phosphor imaging rat studies reported increased brain dopamine D2/3 receptor (DRD2/3) availability following treatment with varenicline, a nicotinergic drug. However, ex vivo studies can only be performed using cross-sectional designs. Small-animal imaging offers the opportunity to perform serial assessments. We evaluated whether high-resolution pinhole single photon emission computed tomography (SPECT) imaging in rats was able to reproduce previous ex vivo findings.
  
  
  METHODS
  Rats were imaged for baseline striatal DRD2/3 availability using ultra-high-resolution pinhole SPECT (U-SPECT-II) and [123I]IBZM as a radiotracer, and randomized to varenicline (n=7; 2 mg/kg) or saline (n=7). Following 2 weeks of treatment, a second scan was acquired.
  
  
  RESULTS
  Significantly increased striatal DRD2/3 availability was found following varenicline treatment compared to saline (time⁎treatment effect): posttreatment difference in binding potential between groups corrected for initial baseline differences was 2.039 (P=.022), indicating a large effect size (d=1.48).
  
  
  CONCLUSIONS
  Ultra-high-resolution pinhole SPECT can be used to assess varenicline-induced changes in DRD2/3 availability in small laboratory animals over time. Future small-animal studies should include imaging techniques to enable repeated within-subjects measurements and reduce the amount of animals.
authors.affiliation: Department of Psychiatry and Amsterdam Institute for Addiction Research, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands. c.l.crunelle@amc.uva.nl
authors.forename: Cleo L
authors.initials: CL
authors.lastname: Crunelle
authors.forename: Tim C
authors.initials: TC
authors.lastname: de Wit
authors.forename: Kora
authors.initials: K
authors.lastname: de Bruin
authors.forename: Ruud M
authors.initials: RM
authors.lastname: Ramakers
authors.forename: Frans
authors.initials: F
authors.lastname: van der Have
authors.forename: Freek J
authors.initials: FJ
authors.lastname: Beekman
authors.forename: Wim
authors.initials: W
authors.lastname: van den Brink
authors.forename: Jan
authors.initials: J
authors.lastname: Booij
mesh_terms: D000818:Animals; D001549:Benzamides; D001552:Benzazepines / Q000494:pharmacology*; D008297:Male; D017072:Neostriatum / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D018722:Nicotinic Agonists / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011759:Pyrrolidines; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon; D000068580:Varenicline
chemical_list: D001549:Benzamides; D001552:Benzazepines; D018722:Nicotinic Agonists; D011759:Pyrrolidines; D011810:Quinoxalines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D000068580:Varenicline