FIGURE 5.

MC1R^e/e mice are more susceptible to dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Adult (6–8-month-old) MC1R^e/e and littermate wildtype (WT) mice were injected intraperitoneally (i.p.) with 20mg/kg MPTP-HCl or control vehicle (saline) once daily for 4 days and sacrificed 7 days after the last MPTP administration. (A) Dopamine (DA) in the striatum measured by high-performance liquid chromatography (HPLC) and DA turnover rate (homovanillic acid [HVA]/DA ratio, HVA determined by HPLC) in MPTP or vehicle control (CON) MC1R^e/e mice and WT littermates (n=6, WT and MC1R^e/e CON; n=8 and 7, WT and MC1R^e/e MPTP). *p< 0.05 versus WT CON; #p < 0.05, ##p< 0.01 versus WT MPTP, 1-way analysis of variance (ANOVA) followed by Tukey post hoc test. (B) Substantial loss of TH-positive neurons in the substantia nigra (SN) of an MC1R^e/e mouse after MPTP subacute treatment. (C) Stereological quantification of nigral tyrosine hydroxylase (TH)- positive neurons expressed as absolute counts and percentage of CON group in MC1R^e/e mice and WT littermates (n=6, WT and MC1R^e/e CON; n=8 and 7, WT and MC1R^e/e MPTP). **p< 0.01versus WT CON; #p< 0.05, ##p< 0.01 versus WT MPTP, 1-way ANOVA followed by Tukey post hoc test for absolute counts and Student t test for normalized counts. (D) Striatal 1 methyl-4-phenylpyridinium (MPP⁺) detected by HPLC in MC1R^e/e and littermate WT mice following 20mg/kg MPTP-HCl intraperitoneal administration (n=6 and 8, WT and MC1R^e/e, both 90 minutes and 6 hours). [Color figure can be viewed at wileyonlinelibrary.com]