Full rescue of the HVA/5-HIAA ratio was observed for treated DAT-KO mice to levels comparable to those observed in WT mice (one-way ANOVA F (2,14) = 9.77, p = 0.0022; Holm-Sidak post-hoc p = 0.414 Fig. 4F).
When compared to the KO control group, the distance travelled by treated DAT-KO mice was significantly different from Day 12 up to Day 48 after surgery (two-way ANOVA F 4,172) = 9.004, p < 0.0001; Bonferroni post-hoc, p < 0.0001 Fig. 5B).
Secondly, we treated DAT-KO mice with d-amphetamine.
As seen in Figure 3, the SWIP response phenotype increased in wild-type animals that were pretreated with fluoxetine but decreased in similarly treated dat-1 (ok157) animals.
Fluoxetine can also aggressively inhibit any transport of dopamine by the serotonin transporters (Bymaster et al. 2002) so that treated dat-1 animals would show a reduced SWIP response, analogous to the reduced response of dat-1 ; dop-3 animals (McDonald et al., 2007).
The interesting observation that pramipexole down-regulated DAT-IR in saline treated mice suggests that DAT regulation plays a role in neuroprotective effects of pramipexole.
(D) Performance of treated and control DAT-KO mice in the Porsolt forced swim test.
Also, the activity of phenylalanine ammonia-lyase (PAL), a critical enzyme in lignin synthesis, initially increased in heat treated pericarp at 1 DAT but subsequently fell into the same level as in the control.
(A) DAT-KO treated mice showed reduction in total distance traveled in 1 hour in the open field starting at Day 24 after surgery.
TH-iCre-AAV was stereotaxically co-infused with CMV-DIO-mDAT-AAV in the DAT-KO treated group, or with CMV-DIO-tdTOMATO-AAV for the KO control group.
For the DAT-KO control group, the AAV construct bore the tdTOMATO gene sequence (CMV-DIO-tdTOMATO-AAV, magenta arrow), while for the DAT-KO treated group, the AAV bore the inverted sequence of the mouse Dopamine Transporter (mDAT) gene, depicted with a teal arrow (CMV-DIO-mDAT-AAV).
