Evaluation of RGS4 selectivity of CCG-203920 in mice
As we previously reported (Blazer et
al. , 2015) that RGS4 inhibitors reverse raclopride-induced akinesia in
the bar and drag tests (Marti et
al. , 2004; Viaro et al. , 2008),
the same tests were used to monitor motor activity in 5
RGS4-/- mice and 5 wild-type controls treated with 1
mg kg-1 (i.p.) raclopride and, 30 min later, by 10 mg
kg-1 CCG-203920 or saline (i.p.). Prior to
pharmacological testing, mice were trained daily for a week on the
behavioral tests until their motor performance became reproducible. The
bar (or catalepsy) test measures the ability of the animal to respond to
an externally imposed static posture. Each mouse was placed gently on a
table and the right and left forepaws were placed alternately on blocks
of increasing heights (1.5, 3, and 6 cm). Total time spent on the blocks
(in seconds) by each paw was recorded (cutoff time 20 s per block, 60 s
maximum) and pooled together. The drag test measures the number of steps
made by the animal when gently lifted by the tail (allowing the forepaws
on the table) and dragged backward at a constant speed (about 20 cm
s-1) for a fixed distance (100 cm). The number of
steps made by each forepaw was counted by two separate blinded observers
and average together.