AT-403 inhibited D1 receptor-stimulated pGluR1 phosphorylation in
striatum
The increase of pGluR1 levels is another biochemical correlate of LID in
rodents (Santini et al. , 2007).
GluR1 is a subunit of the glutamate AMPA receptor, which is
physiologically phosphorylated by PKA activated by dopamine via D1
receptors. We therefore investigated whether CCG-203920 potentiates the
ability of AT-403 (0.03 mg kg-1) to modulate pGluR1
levels. As expected, L-Dopa elevated pGluR1 levels in the lesioned
stratum (+52%; t=2.272, df=12; Fig. 7A). However, in contrast to the
effect on ERK, AT-403 alone was able to normalize pGluR1 levels (Fig.
7A), in line with the well-known inhibitory influence of NOP receptors
over canonical D1 signaling. CCG-203920 did not alter the L-Dopa induced
increase (+52%; t=2.239, df=10) or the AT-403-driven normalization of
pGluR1 levels. Again, neither treatments affected total protein amounts
(Fig. 7B).