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.