Next, we showed that AM3506 given immediately after extinction training (Supplementary Figure S2c) did not reduce fear on the retrieval test 10 days later, indicating that augmenting anandamide during post-training consolidation is not sufficient to facilitate extinction (t-test: P>0.05, n = 12) (Figure 1e). An effect of AM3506 on reconsolidation was also ruled out by the finding that drug treatment before fear memory reactivation (and no extinction) (Supplementary Figure S2d) did not reduce fear on a later test (t-test: P>0.05, n = 8) (Figure 1f). Finally, we confirmed that AM3506 reduced fear on a retrieval test only in mice that had been extinguished, by showing that freezing was unaffected by AM3506 treatment before exposure to the extinction context per se (that is, no CS) (VEH = 74±5% freezing, AM = 69±8, t-test: P>0.05, n = 12), and only in mice that had been fear conditioned, by showing normal/negligible freezing in unconditioned mice given AM3506 before extinction (freezing <1% both groups, t-test: P>0.05, n = 6).
