[18F]MPPF and [18F]FDG μPET imaging in rats: impact of transport and restraint stress

EJNMMI Research

Peter Bartenstein¹  Sibylle Ziegler¹  Barbara von Ungern-Sternberg¹  Franz Josef Gildehaus¹  Simon Lindner¹  Matthias Brendel¹  Verena Buchecker²  Ines Koska²  Ann-Marie Waldron²  R. Maarten van Dijk²  Heidrun Potschka² 

[1] Department of Nuclear Medicine, University Hospital of Munich, Ludwig-Maximilians-University, Munich, Germany;Institute of Pharmacology, Toxicology and Pharmacy, Ludwig-Maximilians-University, Königinstr. 16, 80539, Munich, Germany;

关键词: Distress;    5-HT receptor;    Brain glucose metabolism;    Micro-PET;    Behavior;    Animal model;   

DOI  :  10.1186/s13550-020-00693-3

来源: Springer

【 摘 要 】

BackgroundStress exposure can significantly affect serotonergic signaling with a particular impact on 5-HT1A receptor expression. Positron emission tomography (PET) provides opportunities for molecular imaging of alterations in 5-HT1A receptor binding following stress exposure. Considering the possible role of 5-HT1A receptors in stress coping mechanisms, respective imaging approaches are of particular interest.Material and methodsFor twelve consecutive days, Sprague Dawley rats were exposed to daily transport with a 1 h stay in a laboratory or daily transport plus 1 h restraint in a narrow tube. Following, animals were subjected to μPET imaging with 2′-methoxyphenyl-(N-2′-pyridinyl)-p-[18F]fluoro-benzamidoethylpiperazine ([18F]MPPF) and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). Behavioral and biochemical parameters were analyzed to obtain additional information.ResultsIn rats with repeated transport, hippocampal [18F]MPPF binding exceeded that in the naive group, while no difference in [18F]FDG uptake was detected between the groups. A transient decline in body weight was observed in rats with transport or combined transport and restraint. Thereby, body weight development correlated with [18F]MPPF binding.ConclusionsMild-to-moderate stress associated with daily transport and exposure to a laboratory environment can trigger significant alterations in hippocampal binding of the 5-HT1A receptor ligand [18F]MPPF. This finding indicates that utmost care is necessary to control and report transport and associated handling procedures for animals used in μPET studies analyzing the serotonergic system in order to enhance the robustness of conclusions and allow replicability of findings. In view of earlier studies indicating that an increase in hippocampal 5-HT1A receptor expression may be associated with a resilience to stress, it would be of interest to further evaluate 5-HT1A receptor imaging approaches as a candidate biomarker for the vulnerability to stress.

【 授权许可】

CC BY