Molecular Imaging and Biology

, Volume 17, Issue 4, pp 521–528 | Cite as

Perturbed Development of Striatal Dopamine Transporters in Fatty Versus Lean Zucker Rats: a Follow-up Small Animal PET Study

  • Paul Cumming
  • Simone Maschauer
  • Patrick J. Riss
  • Eva Grill
  • Monika Pischetsrieder
  • Torsten Kuwert
  • Olaf Prante
Original Article

Abstract

Purpose

Post-synaptic dopamine D2/3 receptors are reduced in animal models of obesity, and in obese humans, concordant with similar findings in habitual drug users. However, corresponding pre-synaptic changes in brain dopamine are less documented in obesity models. Therefore, we used positron emission tomography (PET) with the dopamine transporter (DAT) ligand N-(3-[18F]fluoropropyl)-2-β-carbomethoxy-3-β-(4′-methylphenyl) tropane ([18F]FP-CMT) to test the hypothesis that DAT availability is attenuated in adult fatty Zucker (FZ) rats versus lean littermates (LZ).

Procedures

Groups of nine FZ and LZ rats were examined by [18F]FP-CMT PET at approximately 6 weeks and at 6 months of age.

Results

The baseline mean striatal binding potential (BPND) of [18F]FP-CMT did not differ between groups (LZ 2.4; FZ 2.5), although FZ rats already had higher body weight and elevated blood triglycerides, cholesterol, and insulin. At follow-up, a mixed effects multiple regression model showed that the maturation of DAT availability was attenuated in FZ rats, such that the mean BPND in striatum was 17 % lower (LZ 4.0; FZ 3.3; p = 0.01). Body weight was twofold higher in the adult FZ rats, and triglycerides fourfold increased, but glucose remained normal despite doubling of insulin levels.

Conclusions

Maturation of the striatal dopamine innervation is impaired in this model of obesity/hyperlipidaemia without diabetes, implying an acquired trait of reduced dopamine reuptake capacity.

Key words

Dopamine transporters DAT Positron emission tomography Striatum Obesity Zucker rats 

Notes

Acknowledgments

This study is part of the Neurotrition Project, which is supported by the Emerging Fields Initiative (EFI) of the Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU). We thank Manuel Geisthoff for expert technical support. For performing the insulin assays, we thank Dr Christof Schöfl and Jürgen Kressel (Division of Endocrinology and Diabetes, Department of Medicine 1, FAU, Erlangen, Germany).

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

11307_2014_811_MOESM1_ESM.pdf (319 kb)
ESM 1 (PDF 318 kb)

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Copyright information

© World Molecular Imaging Society 2014

Authors and Affiliations

  • Paul Cumming
    • 1
  • Simone Maschauer
    • 1
  • Patrick J. Riss
    • 2
  • Eva Grill
    • 3
  • Monika Pischetsrieder
    • 4
  • Torsten Kuwert
    • 1
  • Olaf Prante
    • 1
  1. 1.Department of Nuclear Medicine, Molecular Imaging and RadiochemistryFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)ErlangenGermany
  2. 2.Kjemisk InstituttUniversitetet i OsloOsloNorway
  3. 3.Institute for Medical Information Processing, Biometry and Epidemiology, and German Center for Vertigo and Balance DisordersLudwig-Maximilians Universität MünchenMunichGermany
  4. 4.Department of Chemistry and Pharmacy, Food Chemistry Division, Emil Fischer CenterFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)ErlangenGermany

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