Figure 2. Striatal dopaminergic denervation induced by bilateral 6-OHDA lesion of the SNc leads to apathetic-like behavior and fine motor dysfunctions.

(A) A PDP total score, as the sum of histological and behavioral components, was assigned to each animal, from 0 (sham-operated animal) to 3 to 7 (prodromal-like animal) or 8 to 12 (clinical-like animal). (B) Examples of TH-stained coronal sections of sham-operated and 6-OHDA rat brains at 3 striatal levels with respect to bregma and corresponding diagrams selected from the atlas of Paxinos and Watson (79), with areas used for quantification of dopaminergic denervation. Scale bar: 2 mm. (C) Quantification of TH-IR staining loss at the striatal levels shown in B, expressed as a percentage of the mean value obtained for sham-operated animals (n = 22). We observed a large decrease of TH-positive neurons in DS and a lighter decrease in Nacc of prodromal (n = 14) and clinical-like (n = 15) rats. (D) 6-OHDA SNc lesion induced an abrupt instrumental deficit in an operant sucrose self-administration procedure. Results are expressed as the mean number of sucrose deliveries per session. Sham-operated rats (n = 22); prodromal-like rats (n = 14); clinical-like rats (n = 15). (E) 6-OHDA SNc lesion reduced the number of adjusting steps in a stepping procedure only in clinical-like animals. Results are expressed as the mean number of forelimb adjustments for 2 trials before (left bars) and after (right bars) 6-OHDA (prodromal-like (n = 14) and clinical-like (n = 15) animals or saline (sham) injection (n = 22). Data are presented as mean ± SEM and were determined by 1-way ANOVA or RM-ANOVA followed by Tukey’s post hoc or Šidák’s test. ***P ≤ 0.001, compared with sham-operated animals; ^##P ≤ 0.01, clinical-like compared with prodromal-like; ^#P < 0.05; ^§§§P ≤ 0.001, before surgery compared with after surgery.