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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 2/2014

01-02-2014 | Original Article

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

Authors: Cindy Casteels, Nathalie Gérard, Kris van Kuyck, Lies Pottel, Bart Nuttin, Guy Bormans, Koen Van Laere

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 2/2014

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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 p cluster < 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 %; p cluster < 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.
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Metadata
Title
Small animal PET imaging of the type 1 cannabinoid receptor in a rodent model for anorexia nervosa
Authors
Cindy Casteels
Nathalie Gérard
Kris van Kuyck
Lies Pottel
Bart Nuttin
Guy Bormans
Koen Van Laere
Publication date
01-02-2014
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 2/2014
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-013-2522-8

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