FIGURE 4.

MC1R^e/e mice are more susceptible to dopaminergic toxin 6-hydroxydopamine (6-OHDA). (A) Adult (6–8-month-old) MC1R^e/e and littermate wild-type (WT) mice were infused with 10μg 6-OHDA into the left striatum. Rotational behavior was assessed at 3 weeks, and animals were sacrificed at 4 weeks after 6-OHDA lesion. (B) Spontaneous and 5mg/kg amphetamine-induced net ipsilateral rotations in MC1R^e/e mice and littermate WT controls (n=12, WT and MC1R^e/e). *p< 0.05 versus WT by Student t test. (C) Striatal dopamine (DA) measured by high-performance liquid chromatography (HPLC) and DA turnover rate (homovanillic acid [HVA]/DA ratio, HVA determined by HPLC) on contralateral (Contra) unlesioned side and ipsilateral (Ipsi) lesioned side in MC1R^e/e mice and WT littermates (n=12, WT and MC1R^e/e). **p < 0.01 versus WT Contra side; ##p< 0.01 versus WT Ipsi side, 1-way analysis of variance (ANOVA) followed by Tukey post hoc test. (D) Disruption of substantia nigra (SN) dopaminergic neurons (stained positive for tyrosine hydroxylase [TH]) on the Ipsi lesioned side of an MC1R^e/e mouse after 6-OHDA lesion. (E) Stereological quantification of nigral TH-positive neurons expressed as absolute counts and percentage of Contra side in MC1R^e/e mice and WT littermates (n=12,WT and MC1R^e/e). **p< 0.01 versus WT Contra side; ##p< 0.01 versus WT Ipsi side, 1-way ANOVA followed by Tukey post hoc test for absolute counts and Student t test for normalized counts. [Color figure can be viewed at wileyonlinelibrary.com]