Varenicline increases in vivo striatal dopamine D2/3 receptor binding: an ultra-high-resolution pinhole [123I]IBZM SPECT study in rats

Nucl Med Biol. 2012 Jul;39(5):640-4. doi: 10.1016/j.nucmedbio.2011.11.006. Epub 2012 Jan 20.


Introduction: 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.

MeSH terms

  • Animals
  • Benzamides*
  • Benzazepines / pharmacology*
  • Male
  • Neostriatum / diagnostic imaging*
  • Neostriatum / drug effects
  • Neostriatum / metabolism*
  • Nicotinic Agonists / pharmacology
  • Protein Binding / drug effects
  • Pyrrolidines*
  • Quinoxalines / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3 / metabolism*
  • Tomography, Emission-Computed, Single-Photon*
  • Varenicline


  • Benzamides
  • Benzazepines
  • Nicotinic Agonists
  • Pyrrolidines
  • Quinoxalines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • 3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide
  • Varenicline