Fig. 4

Acute blockade of LRRK2 kinase activity does not affect striatal dopamine (DA) levels whereas acute DAT blockade evoked blunted neurochemical and behavioral responses in G2019S knock-in (KI) mice in vivo. Microdialysis was performed in the dorsolateral striatum of 19-month-old G2019S KI mice and with age-matched wild-type (WT) littermates (WT) (a, b). Mice were then challenged with the LRRK2 kinase inhibitor Nov-LRRK2-11 (10 mg/kg, i.p.) or the DAT blocker GBR-12783 (20 mg/kg, i.p.). Dialysate levels of DA are expressed as absolute values (nM) and are mean ± SEM of 5 WT and 6 G2019S KI mice (a), or 6 WT and 9 G2019S KI mice (b). Motor responses of 12-month-old mice to GBR-12783 (6 mg/kg, i.p.) or saline administration (c-e). Motor activity was assessed using the bar (c), drag (d) and rotarod (e) tests, before (baseline) and after (20 and 90 min) drug administration, and was expressed as percentage of performance at baseline. Data are means ± SEM of 12–17 (WT) or 13–17 (G2019S KI) mice per group. Statistical analysis was performed using one-way RM ANOVA (a-b) or conventional ANOVA (c-e) followed by the Newman–Keuls test for multiple comparisons. *p < 0.05, ** p < 0.01 significantly different from baseline values; ^# p < 0.05, ^## p < 0.01 significantly different from saline