Fig. 3.
PET and BPND analysis indicate striatal DA release upon DREADD-based stimulation of PPN cholinergic neurons. (A) Representative PET/CT images at the level of the striatum, pre- (left) and post-CNO (right) in a representative lesioned (top row images) and sham-lesioned control rat (bottom row images). The toxin/sham-lesioned area is indicated by the white arrowhead. For each panel, the TACs of the right (contralesional) and left (ipsilesional) striata are reported, along with the SRTM BPND estimates obtained using the cerebellum as reference region. During CNO OFF, higher [11C]PHNO BPND values were found within left (ipsilesioned) striata compared with right (contralesioned) striata; receptor occupancy estimates were comparable at CNO ON. (B) BPND estimates in the ipsilesional and (C) contralesional striata for lesioned rats at CNO OFF (n = 6) and CNO ON (n = 6), as well as sham control rats (CNO OFF: n = 4; CNO ON: n = 4). In hemi-lesioned rats, BPND estimates were reduced in both the ipsilesional and contralesional sides during CNO ON compared with baseline; the reduction was particularly striking on the lesioned hemispheric side. No notable change in BPND estimates was seen between CNO OFF and CNO ON for sham rats. (D) Left-to-right [11C]PHNO striatal SUV ratios (normalized to the cerebellum) were significantly higher pre-CNO in lesioned versus sham rats (*p = 0.02). In lesioned rats, at CNO ON, there was a significant decrease in the L:R striatal SUV ratio compared with CNO OFF (*p = 0.017). Error bars depict SEM throughout