CCG-203920 extended the antidyskinetic effect of AT-403
In a previous study, we described the dose-dependent antidyskinetic
effect of AT-403 in the 6-OHDA rat model of LID in vivo
(Arcuri et al. , 2018). At the
highest dose tested AT-403 (0.1 mg kg-1) exerted
strong sedative effects that overlapped the antidyskinetic effect.
Conversely, at the dose of 0.03 mg kg-1, AT-403
exerted a mild and transient antidyskinetic effect in the absence of
sedation. Here, in the same model, to improve the antidyskinetic effect
of this AT-403 dose, we challenged AT-403 (0.03 mg
kg-1 s.c.) with L-Dopa (6 mg kg-1 +
benserazide 15 mg
kg-1 s.c.) in the presence and in the absence of
CCG-203920 10 mg kg-1 (Fig. 5A). AT-403 alone delayed
the onset of AIMs by 40 min, without affecting the overall duration and
severity of the response. Co-administration of CCG-203920 caused a
further 20 min delay in AIM appearance, without significantly affecting
the overall response to AT-403 (Fig. 5A), suggesting that RGS4 blockade
potentiates NOP agonist induced antidyskinetic effects (significant
effect of time F8,432=37.00, treatment
F3,432=6.86, and time x treatment interaction
F24,432=43.06).