Age related changes in the dopamine system of the Sprague-Dawley rat measured via positron emission tomography

249 Objectives Positron emission tomography (PET) allows the performance of longitudinal in-vivo studies. In order to correctly interpret longitudinal results, it is important to understand aging effects on tracers’ binding parameters, such as tissue input binding potential BPND. In this retrospective study we evaluate the effect of age on BPND values for three tracers related to the dopaminergic (DA) system in Sprague-Dawley rats. Methods DA neuronal terminal integrity was monitored using (+)-11C-dihydrotetrabenazine (DTBZ), DA transporter density using 11C-methylphenidate (MP), and binding to D2/3-DA receptors using 11C-raclopride (RAC). Cross-sectional data were compiled from healthy rats, and from the contralateral striatum of unilaterally 6-OHDA lesioned rats (imaged a minimum of 1 month post-lesion), at 3 to 24 months of age. Data were collected on the Siemens microPET Focus120. BPND values were extracted from the reconstructed images using regions of interest placed on the striatum and cerebellum (reference region) using the Logan graphical method. Results No correlation was found between age and DTBZ BPND (average BPND 4.0±0.4, n=58). A significant negative correlation was found between age and BPND for both the MP (p=0.017, linear relationship, n=36) and RAC (p Conclusions PET imaging in the rat brain is sensitive to age related changes in the DA transporter and D2/3-DA receptors, therefore longitudinal imaging studies with RAC and MP should be designed to control for age related changes. Conversely, longitudinal studies carried out with DTBZ may be simplified due to the lack of an age effect. Research Support Natural Sciences and Engineering Research Council, Canadian Institutes of Health Research, Michael Smith Foundation for Health Research