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. 2013 Nov 26;289(1):264–274. doi: 10.1074/jbc.M113.495499

FIGURE 2.

FIGURE 2.

CPA recordings of the evoked DA efflux and action of cocaine, methylphenidate, and nomifensine in the striata of DAT-CI mice. A, traces showing the effects of cocaine (Coca) (10 μm) at the different time points indicated below. The histogram on the left indicates the effect of cocaine on DA overflow. Note that cocaine (0.3 μm) did not change the amplitude of the signal that was instead decreased by 1–100 μm drug (by 1 ± 1% at 0.3 μm (n = 4, p = 0.544 F (0.41), one-way ANOVA), by 17 ± 7% at 1 μm (n = 6, p = 0.029 F (6.39), one-way ANOVA), by 33 ± 2% at 3 μm (n = 14, p = 3.657E-7 F (75.44), one-way ANOVA), by 57 ± 2% at 10 μm (n = 49, p = 0 F (860.53), one-way ANOVA), by 85 ± 2% at 30 μm (n = 19, p = 0 F (1931), one-way ANOVA), and by 93 ± 1% at 100 μm (n = 4, p = 1.659E-9 F (60127), one-way ANOVA)). The histogram on the right indicates that cocaine reduces the decay phase of the DAergic signal by 1 ± 3% with 0.3 μm (n = 4, p = 0.805 F (0.07), one-way ANOVA), by 7 ± 1% with 1 μm (n = 6, p = 0.082 F (3.73), one-way ANOVA), by 13 ± 2% with 3 μm (n = 14, p = 0.0008 F (14.21), one-way ANOVA), by 21 ± 2% with 10 μm (n = 49, p = 0 F (126.25), one-way ANOVA), by 46 ± 8% with 30 μm (n = 19, p = 1.11E-16 F (123.30), one-way ANOVA), and by 99 ± 1% with 100 μm (n = 4 p = 6.991E-9 F (29290), one-way ANOVA). Ctrl, control. (*, p < 0.05; ***, p < 0.001). B, the histogram on the left indicates the effect of methylphenidate on DA overflow. Note the decrease of the amplitude caused by 3 μm (by 4 ± 1%, n = 7, p = 0.014 F (8.19), one-way ANOVA), at 10 μm (by 16 ± 2%, n = 8, p = 0.001 F (15.65), one-way ANOVA), and at 30 μm (by 29 ± 4%, n = 4, p = 0.002 F (47.46), one-way ANOVA). The histogram on the right indicates that methylphenidate decreases the decay phase of the DAergic signal by 1 ± 1% with 3 μm (n = 7, p = 0.298 F (1.17), one-way ANOVA), by 9 ± 1% with 10 μm (n = 8, p = 0.0001 F (27.59), one-way ANOVA), and by 38 ± 4% with 30 μm (n = 4, p = 0.0004 F (116.32), one-way ANOVA) (*, p < 0.05; **, p < 0.01; ***, p < 0.001). C, the histogram on the left indicates the effect of nomifensine on DA overflow. Nomifensine increase the amplitude of the signal when superfused at the different concentrations by 31 ± 13% at 0.3 μm (n = 8, p = 0.029 F (5.90), one-way ANOVA), by 58 ± 5% at 1 μm (n = 20, p = 4.393E-13 F (115.58), one-way ANOVA), by 88 ± 19% at 10 μm (n = 5, p = 0.001 F (20.78), one-way ANOVA), and by 56 ± 17% at 30 μm (n = 8, p = 0.004 F (11.14), one-way ANOVA). The histogram on the right indicates that nomifensine increases the decay phase of the DAergic signal by 46 ± 18% with 0.3 μm (n = 8, p = 0.0002 F (24.35), one-way ANOVA), by 83 ± 9% with 1 μm (n = 20, p = 4.577E-11 F (82.57), one-way ANOVA), by 130 ± 46% with 10 μm (n = 10, p = 0.02 F (11.42), one-way ANOVA), and by 358 ± 43% with 30 μm (n = 8, p = 0.0002 F (24.15), one-way ANOVA). Note that the increase in the amplitude of the DAergic signal in the DAT-CI mice caused by nomifensine is almost half of that evoked in wild-type animals. (*, p < 0.05; **, p < 0.01; ***, p < 0.001).