Extended Data Fig. 9: After unilateral lesion of SNc dopamine cells, l-DOPA and dopamine agonists induce a contralateral turning bias, and l-DOPA can also induce dyskinesia.

a–c, Time traces showing mean ± s.e.m. effects of different doses of l-DOPA, SKF81297 and quinpirole on the contralateral rotational bias of mice, scored in 20-min time bins, >14 days after unilateral 6-OHDA lesion. All drug doses had their maximal behavioural effects approximately 30 min after drug administration. All dose–time interactions differed significantly from vehicle treatment (P < 5 × 10⁻³), and the effects of l-DOPA and SKF81297 were dose-dependent (P < 5 × 10⁻³). Two-way, repeated-measures ANOVA. d, Time traces of the mean ± s.e.m. mouse rotational bias for the three different drugs in a–c, at doses of each drug that induce comparable levels of rotational bias during the time window used in our studies for Ca²⁺ imaging (shaded in grey), during which we assessed the effects of these drugs on dSPN and iSPN activity in parkinsonian mice (Fig. 4). e, Comparison of the net rotational bias in the first 40 min after administration of the three drugs at the same doses as in d. Note that, as assessed by their effects on turning behaviour, these three compounds were statistically indistinguishable at these doses. ‘ns’ denotes P > 0.2 for comparisons between drugs; n = 13 mice; Wilcoxon signed-rank test. However, all drugs had significant effects relative to vehicle treatment. **P < 5 × 10⁻³; Wilcoxon signed-rank test; n = 13 mice. f–i, Time traces showing how different dosages of l-DOPA affect the mean ± s.e.m. axial (f), orofacial (g), limb (h) and total (i) AIMS values, a behavioural measure of dyskinesia in preclinical models of Parkinson’s disease³¹. All three l-DOPA doses had significant effects compared to vehicle treatments (P < 0.02; two-way ANOVA) and differed significantly in their effects at the different dosages (P < 0.05). As in d, the grey shading in i denotes the time window used for Ca²⁺ imaging (Figs. 4, 5). j, l-DOPA increased the peak total AIMS values, in a dose-dependent manner, in the first 40-min after mice received the l-DOPA doses in f–i. *P < 0.05, **P < 5 × 10⁻³; Wilcoxon signed-rank test. Error bars in a–d and f–i indicate s.e.m. All data in a–j are from a distinct cohort of n = 13 freely moving mice not subject to the protocol of Fig. 1a.