European Journal of Nuclear Medicine and Molecular Imaging

, Volume 41, Issue 2, pp 308–321

Small animal PET imaging of the type 1 cannabinoid receptor in a rodent model for anorexia nervosa

Authors

    • Division of Nuclear MedicineUniversity Hospital and KU Leuven
    • Molecular Small Animal Imaging Center (MoSAIC)KU Leuven
  • Nathalie Gérard
    • Division of Nuclear MedicineUniversity Hospital and KU Leuven
    • Molecular Small Animal Imaging Center (MoSAIC)KU Leuven
  • Kris van Kuyck
    • Laboratory for Experimental Functional NeurosurgeryKU Leuven
  • Lies Pottel
    • Division of Nuclear MedicineUniversity Hospital and KU Leuven
    • Molecular Small Animal Imaging Center (MoSAIC)KU Leuven
  • Bart Nuttin
    • Laboratory for Experimental Functional NeurosurgeryKU Leuven
  • Guy Bormans
    • Molecular Small Animal Imaging Center (MoSAIC)KU Leuven
    • Laboratory for RadiopharmacyUniversity Hospital and KU Leuven
  • Koen Van Laere
    • Division of Nuclear MedicineUniversity Hospital and KU Leuven
    • Molecular Small Animal Imaging Center (MoSAIC)KU Leuven
Original Article

DOI: 10.1007/s00259-013-2522-8

Cite this article as:
Casteels, C., Gérard, N., van Kuyck, K. et al. Eur J Nucl Med Mol Imaging (2014) 41: 308. doi:10.1007/s00259-013-2522-8

Abstract

Purpose

Several lines of evidence strongly implicate a dysfunctional endocannabinoid system (ECS) in eating disorders. Using [18F]MK-9470 and small animal positron emission tomography (PET), we investigated for the first time cerebral changes in type 1 cannabinoid (CB1) receptor binding in vivo in the activity-based rat model of anorexia (ABA), in comparison to distinct motor- and food-related control conditions and in relation to gender and behavioural variables.

Methods

In total, experiments were conducted on 80 Wistar rats (23 male and 57 female). Male rats were assigned to the cross-sectional conditions: ABA (n = 12) and CONTROL (n = 11), whereas female rats were divided between two settings: (1) a cross-sectional design using ABA (n = 13), CONTROL (n = 9), and two extra control conditions for each of the variables manipulated in ABA, i.e. DIET (n = 8) and WHEEL (n = 9), and (2) a longitudinal one using ABA (n = 10) and CONTROL (n = 8) studied at baseline, during the model and upon recovery. The ABA group was subjected to food restriction in the presence of a running wheel, the DIET group to food restriction without wheel, the WHEEL group to a normal diet with wheel and CONTROL animals had a normal diet and no running wheel. Parametric CB1 receptor images of each group were spatially normalized to Paxinos space and analysed voxel-wise.

Results

In the ABA model, absolute [18F]MK-9470 binding was significantly increased in all cortical and subcortical brain areas as compared to control conditions (male +67 %; female >51 %, all pcluster < 6.3×10−6) that normalized towards baseline values after weight gain. Additionally, relative [18F]MK-9470 binding was increased in the hippocampus, inferior colliculus and entorhinal cortex of female ABA (+4.6 %; pcluster < 1.3×10−6), whereas no regional differences were observed in male subjects. Again, relative [18F]MK-9470 binding values normalized upon weight gain.

Conclusion

These data point to a widespread transient disturbance of the endocannabinoid transmission, specifically for CB1 receptors in the ABA model. Our data also suggest (1) gender effects on regional CB1 receptor binding in the hippocampus and (2) add further proof to the validity of the ABA model to mimic aspects of human disease.

Keywords

Type 1 cannabinoid receptorAnorexia nervosaABASmall animal PET[18F]MK-9470

Supplementary material

259_2013_2522_MOESM1_ESM.tif (553 kb)
High resolution image (TIFF 552 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013