Figure 2.

CBD reversed cue-induced anxiety in the light/dark test (A) and open field (B) after multiple cue-shock pairings. Twenty-four hours after the last conditioning session, the cue elicited anxiety in the light/dark box as measured by increased latency to enter the light side of the box (A; cue*drug-F(1,42)=9.270, p=0.004; veh-neutral vs veh-cue, q(42)=5.885, p=0.0009; veh-cue vs CBD-cue, q(42)=5.794, p=0.001; CBD-neutral vs veh-cue, q(42)=5.460, p=0.0021), fewer entries made into the light side of the box, and less time spent on the light side (A; entries-cue*drug, F(1,44)=5.887, p=0.0194; duration-cue*group-F(1,44)=4.540, p-0.039). Two weeks later, the cue continued to increased avoidance behavior in the open field, with vehicle cue animals showing fewer entries and time spent in the center of the field (B). Vehicle cue rats exhibited an increased composite anxiety Z score which was reversed by CBD (C; cue*group-F(1,7)=11.92, p= 0.017; veh-neutral vs veh-cue, q(7)=5.702, p=0.02, d=1.63; veh-cue vs CBD-cue, q(7)=5.196, p=0.031, d=1.45; CBD-neutral vs veh-cue- q(7)=6.061, p=0.015, d=1.66). Bars and error bars represent means +/− the standard error of the mean. *p<0.05, **p<0.01, ***p<0.001.