Fig. 4

Fast scan cyclic voltammetry of evoked extracellular dopamine release and reuptake. a Example of average peak for each genotype, indicating greater response and slower decay in slices from VKI animals. On the top right corner, examples of the voltammograms for dopamine detection showing oxidation and reduction of dopamine, one for each genotype and calibrations (0.5 and 1 µM) used at the end of the recording each day. b A series of increasing intensity single pulse stimuli were delivered every 2 min to obtain an input/output curve. VKI slices showed an increase in evoked dopamine as compared to slices from their WT littermates (2-way ANOVA interaction F_12,588 = 3.871, p < 0.0001, input F_6,588 = 87.54, p < 0.0001, genotype F_2,98 = 7.097, p < 0.05, subject F_98,588 = 29.35, p < 0.0001; Bonferroni post-test WT vs Het ^*p < 0.05, ^**p < 0.01^***, p < 0.001^****, p < 0.0001, WT vs Homo; ^#p < 0.05, ^##p < 0.01, ^###p < 0.001). c At stimulation intensities leading to 50–70% maximum dopamine release, based on the input/output, a series of 3 pulses were given with an interval of 2 min between each. With this paradigm the single pulse average was also greater in slices from Het and Homo mice (1-way ANOVA F_2,59 = 6.937, p < 0.05, Bonferroni post-test WT vs Het t₍₉₈₎ = 2.284, p < 0.05, WT vs Homo t₍₉₈₎ = 3.70, p < 0.001). d Decay times were slower in Het and Homo VKI slices (1-way ANOVA F_2,98 = 4.373, p < 0.02, Bonferroni post-test t₍₉₈₎ = 2.706 p < 0.05, and t₍₉₈₎ = 2.424, p < 0.05 for Het and Homo VKI slices, respectively). e VKI slices were comparable to WT in paired-pulse recordings applied 4 s apart (1-way ANOVA F_2,77 = 1.36, p = 0.26). f Application of the D2 agonist quinpirole (50 nM) in WT slices resulted in a 20–50% reduction in dopamine release within ~5 min. VKI slices showed more rapid D2 inhibition compared to slices from WT littermates (2-way RM-ANOVA, interaction F_10,470 = 1.47, p = 1.42, time F_5,470 = 49.24, p < 0.0001, genotype F_2,94 = 3.769, p < 0.05, subjects F_94,470 = 4.934; Bonferroni post-test WT vs Het ^*p < 0.05, WT vs Homo; ^#p < 0.05^##, p < 0.01). g In a separate cohort, quinpirole (50 nM) treatment for 30 min gave a comparable 40–50% reduction for all genotypes (1-way ANOVA F_2,25 = 1.166, p = 0.33)