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

Background: Stress 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 methods: For 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 mu PET imaging with 2'-methoxyphenyl-(N-2'-pyridinyl)-p-[F-18]fluoro-benzamidoethylpiperazine ([F-18]MPPF) and 2-deoxy-24 [F-1(8)]fluoro-D-glucose ([F-18]FDG). Behavioral and biochemical parameters were analyzed to obtain additional information. Results: In rats with repeated transport, hippocampal [F-18]MPPF binding exceeded that in the naive group, while no difference in [F-18]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 [F-18]MPPF binding. Conclusions: Mild-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 [F-18]MPPF. This finding indicates that utmost care is necessary to control and report transport and associated handling procedures for animals used in mu PET 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.