UNC9975 and UNC9994 reduce CAR in βArr2 mice but do not affect associative fear conditioning. Once CAR responses were stable, mice were treated the next day with vehicle (Veh) or a UNC compound, and assessed 30 min later. (a, b) Effects of UNC9975 on CAR responses by WT and βArr2-KO mice. RMANOVA for CAR with UNC9975 revealed a significant within-subjects day effect (F(2, 90)=71.42, p<0.001) and a significant day-by-treatment interaction (F(4, 90)=15.70, p<0.001). In addition, the between-subjects effect of treatment was significant (F(2, 45)=12.56, p<0.001). (c, d) Effects of UNC9994 on CAR responses by WT and βArr2-KO mice. RMANOVA for CAR with UNC9994 demonstrated a significant within-subjects day effect (F(2, 62)=36.34, p<0.001) and significant day-by-treatment (F(2, 62)=26.00, p<0.001) and day-by-treatment-by-genotype interactions (F(2, 62)=4.10, p=0.021). The between-subjects treatment effect was significant (F(1, 31)=22.22, p<0.001); the effects of genotype (F(1, 31)=3.38, p=0.076) and the treatment-by-genotype interaction (F(1, 31)=3.60, p=0.067) were marginally significant. (e, f) Effects of UNC9975 on fear conditioning in WT and βArr2-KO mice. RMANOVA at retention testing revealed significant within-subjects effects of time (F(6, 324)=9.89, p<0.001). Base, baseline; CS, conditioned stimulus; ITI, intertrial interval; FC, fear conditioning. N=8–11 mice/genotype/treatment condition. The data are presented as mean±SEM; *p<0.05, WT vs βArr2-KO; #p<0.05, within genotype vs Veh; ‡p<0.05, within genotype vs baseline responses.