Fig. 4.
siRNA-induced specific knockdown of DAT mRNA in the substantia nigra and ventral tegmental area. Mice received a 2-week infusion of vehicle, DAT-targeting siRNA, mmRNA, or GBR-12909 (3 or 30 μg/day) into the dorsal third ventricle. DAT mRNA levels were reduced significantly in the ventral midbrain regions of mice infused with siRNA. Levels of TH mRNA in the same regions were unaffected by any treatment. (A) Low-magnification (×20), dark-field photomicrographs of representatives of in situ hybridization with DAT (Upper) and TH (Lower) riboprobes in adjacent brain sections, after emulsion-dipping of slides. (B) Densitometric quantification of mRNA positive grains is presented as mean OD values ± SEM of 20–24 observations (two to four observations per animal and six animals per group). ***, P < 0.001, significantly different from all other treatments, using one-way ANOVA followed by Tukey's post hoc test.