Figure 7.
Reduction of l-DOPA-induced dyskinesia in Narp KO mice. A, Protein levels of DARPP-32, Gαolf, ERK1/2, Narp, and actin assessed by immunoblotting in the striatum of WT mice (n = 12), homozygous (KO, n = 11), and heterozygous (HT, n = 12) Narp KO mice. A representative immunoblot (right) is presented. The protein levels of DARPP-32, Gαolf, ERK1/2 and actin (left) were not significantly different between genotypes. Data were normalized on WT mice and correspond to the mean + SEM. B, Comparison of dopamine neuron lesion in Narp KO and WT 6-OHDA-lesioned mice. Dopaminergic fiber lesion was assessed by determining the striatal levels of TH by immunoblotting in the lesioned (L) and unlesioned (UL) striatum of the WT (n = 21) and Narp KO (n = 17) mice, previously scored for AIMs. A comparable degree of dopamine denervation was observed in both groups. Data are expressed as means + SEM of percentage of the mean in the unlesioned striata (control). ***p < 0.001, lesioned versus unlesioned side, post hoc test. C, Total AIM score obtained after each period of treatment with l-DOPA at 5, 10, and 20 mg/kg (see Materials and Methods) in 6-OHDA-lesioned WT mice (white boxes, n = 17) and Narp KO mice (black boxes, n = 21). Total AIM scores are the sum of scores obtained every 20 min for 2 h after l-DOPA treatment. Data are expressed as means + SEM. *p < 0.05, KO versus WT, post hoc test. D, Time course of AIM score after l-DOPA (20 mg/kg on day 15 of treatment; see Materials and Methods) in WT mice (white boxes, n = 21) and Narp KO mice (black boxes, n = 27). Data are expressed as means ± SEM. *p < 0.05, KO versus WT, post hoc test.