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. 2017 Dec 20;43(5):1164–1173. doi: 10.1038/npp.2017.254

Figure 5.

Figure 5

Examination of iMSN-D2R-biased signaling pathways in psychomotor drug effects. (a) iMSN-D2KO (n=8) and Cre- (n=8) littermate controls were tested for their locomotor response to 3 mg/kg amphetamine. Amphetamine-induced locomotion was significantly reduced in iMSN-D2KO mice following 3 mg/kg compared with Cre- controls (two-way repeated-measures ANOVA on genotype × time interaction with Bonferroni post hoc tests within time points, ***p<0.001). (b) Next, iMSN-D2AAV-WT (n=10), iMSN-D2AAV-Gprot (n=12), iMSN-D2AAV-βarr (n=12), and iMSN-D2AAV-D80A (n=9) were tested for amphetamine-induced locomotion. iMSN-D2AAV-WT mice showed significant restoration of amphetamine-induced locomotion over iMSN-D2AAV-D80A (two-way repeated-measures ANOVA on viral genotype × time interaction with Bonferroni post hoc tests, *p<0.05 and **p<0.01). iMSN-D2AAV-Gprot and iMSN-D2AAV-βarr mice showed intermediate restoration effects, with no significant difference found between these viral genotypes and iMSN-D2AAV-WT or iMSN-D2AAV-D80A mice. (c) Locomotion was significantly reduced in iMSN-D2KO following 10 mg/kg cocaine (two-way RMANOVA on genotype × time interaction with Bonferroni post hoc tests, ***p<0.001). (d) iMSN-D2AAV-WT (n=6), iMSN-D2AAV-Gprot (n=8), iMSN-D2AAV-βarr (n=8), and iMSN-D2AAV-D80A (n=6) were similarly tested following 10 mg/kg cocaine. The iMSN-D2AAV-WT, iMSN-D2AAV-Gprot, and iMSN-D2AAV-βarr mice all showed significant restoration of cocaine induced locomotion (two-way repeated-measures ANOVA on genotype × time interaction with Bonferroni post hoc tests, **p<0.01 and ***p<0.001). (e) Finally, PCP-induced locomotion was tested in iMSN-D2KO and Cre- mice that was significantly reduced in iMSN-D2KO mice (two-way repeated-measures ANOVA on genotype × time interaction with Bonferroni post hoc tests, *p<0.05 and **p<0.001). (f) iMSN-D2AAV-βarr mice (n=8) showed significant restoration of PCP-induced locomotion over iMSN-D2AAV-D80A mice (n=6) (two-way repeated-measures ANOVA on genotype × time interaction with Bonferroni post hoc tests, *p<0.05 and **p<0.01 Bonferroni post hoc tests). iMSN-D2AAV-WT (n=6) and iMSN-D2AAV-Gprot mice (n=8), however, only showed intermediate restoration, not significantly differing from iMSN-D2AAV-D80A mice. Values represent mean±SEM.