Figure 4: Overexpression of DAT increases the behavioural and neurochemical potency of MPH and releasers. | Nature Communications

Figure 4: Overexpression of DAT increases the behavioural and neurochemical potency of MPH and releasers.

From: Methylphenidate amplifies the potency and reinforcing effects of amphetamines by increasing dopamine transporter expression

Figure 4

(a–c) Rate of dopamine uptake (Vmax; ***P<0.001 versus WT, n=16 WT, 18 DAT-tg, Student’s t-test, unpaired) and stimulated dopamine release ([DA] per pulse; *P<0.05 versus WT, n=16 WT, 18 DAT-tg, Student’s t-test, unpaired) were increased in DAT overexpressing mice (DAT-tg; blue) relative to WT (green). (d–f) MPH- (***P<0.001 versus control, n=5 WT, 6 DAT-tg, two-way ANOVA) and AMPH- (*P<0.05, ***P<0.001 versus control, n=5 WT, 7 DAT-tg, two-way ANOVA), but not cocaine (6 WT, 5 DAT-t), -induced dopamine uptake inhibition was enhanced in the NAc core of DAT-tg mice as compared with WT. (g–i) Locomotor activating effects of MPH (*P<0.05 versus control, n=6 per group, two-way ANOVA) and AMPH (*P<0.05, **P<0.01 versus control, n=7 WT, 8 DAT-tg, two-way ANOVA), but not cocaine (n=8 WT, 6 DAT-tg), were enhanced in DAT-tg mice. (g–i, insets) Saline-induced locomotion over the 60 min testing period was not different between DAT-tg and WT mice. Error bars are reported as mean±s.e.m. DA, dopamine; MPH, methylphenidate; AMPH, amphetamine; Vmax, maximal rate of dopamine uptake; WT, wild-type.

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