Next, to isolate the extinction-facilitating action of AM3506 to CB1Rs within the BLA, we stereotaxically implanted guide cannulae aimed bilaterally at the BLA. After recovering from surgery, mice underwent behavioral testing and pre-extinction systemic AM3506 treatment as above, with half receiving bilateral infusion of 2 μg/μl SR141716 (or equivalent volume of 0.5 μl per hemisphere vehicle) into the BLA 5 min before the systemic AM3506 treatment. Drug treatment did not affect baseline or CS-induced freezing during extinction training (ANOVA effect of treatment: P>0.05, n = 8–10) (Supplementary Figure S6b). Fear was again reduced in AM3506-treated mice, compared to vehicle, during the retrieval test (ANOVA effect of treatment: F2,19 = 3.54, P<0.05, followed by post hoc tests, n = 7–8). The key novel finding, however, was that this extinction-facilitating effect was absent in mice that had received BLA infusion of SR141716 (Figures 3b and c).
