Figure 5.
Reversion of the motivational deficits induced by 6-OHDA SNc lesions by the D3R agonist PD-128907 was blocked by the D3R antagonist SB-277011A, but not by the D2R antagonist L-741626. (a) Representation of the mean number of sucrose deliveries of the three last fixed ratio 1 (FR1) sessions in sham-operated (white histograms) and lesioned (black histograms) animals. Subchronic administration of PD-128907 (0.1 and 0.15 mg kg−1), but not of SKF-38393 (2.5 and 3.5 mg kg−1) or sumanirole (0.1 and 0.15 mg kg−1), improved instrumental performances of the 6-OHDA-lesioned rats. (b) SB-277011A (10 mg kg−1) but not L-741626 (1.5 mg kg−1) blocked specifically this reversal effect of PD-128907 (0.15 mg kg−1) in lesioned rats. (c) PD-128907, but not SKF-38393 or sumanirole enhanced the breakpoint (that is, last ratio completed) of 6-OHDA-lesioned rats after 8 days of sucrose self-administration. (d) A similar effect of PD-128907 (0.15 mg kg−1) was observed after 18 days of sucrose self-administration. Dot lines represented the mean of the instrumental performances of the three last FR1 sessions of vehicle-treated sham animals (a), the mean of the number of sucrose deliveries of vehicle-treated 6-OHDA-lesioned animals during antagonists tests (b) or the mean of the breakpoint of vehicle-treated 6-OHDA-lesioned animals (c–d). *P<0.05; **P<0.01; ***P<0.001, sham-operated versus lesioned within the same treatment and #P<0.05, ##P<0.01, ###P<0.001 between the treatments for sham-operated and lesioned conditions, respectively (n=8–21 per group). 6-OHDA, 6-hydroxydopamine; PD, Parkinson's disease; SNc, substantia nigra pars compacta.