Figure 5. Inhibition of 2-AG hydrolysis enhances learning in a temporal associative memory task. A, Time course of trace conditioning. On day 1, vehicle (black squares) or JZL184 (5 mg/kg; green squares) was administered (intraperiteonally) to animals. Mice were returned to their home cage for 2 h before trace conditioning that consisted of 3 pairs of foot shocks (0.6 mA, 0.5 s) and tones (15 s, 85 db, 2900 hz) presented every 4 min. The JZL184-injected group displayed elevated freezing immediately following tones (gray bars). Freezing was averaged over 1 min during and after the tone. B, Day 2 animals underwent the tone test (no shocks). Gray bars represent tone presentation. B, Right, Average freezing during the first 2 min of the first episode of tone presentation. Animals that had previously been administered JZL184 during training demonstrated elevated tone freezing (p < 0.05; C). On day 3, animals underwent the context test. Freezing was monitored in the original context over 6 min. No difference was observed between the drug and vehicle group. D, Time course of trace fear conditioning in animals administered 0.3 mg/kg (cyan) or 1.0 mg/kg (light blue) URB579 and vehicle (black). No difference was observed in freezing between any of the groups either during training or tone test on day 2 (E, right panel is the average freezing during the first 2 min of the first episode) or context test on day 3 (F). G, Freezing is enhanced in Cre+ mice administered JZL184 during acquisition. H, In the subsequent tone test, there is no difference in tone freezing in vehicle or drug-treated Cre+ mice. I, Freezing during the tone test (after first tone) in Cre− and Cre+ mice. JZL184-treated Cre− mice demonstrated enhanced freezing compared with the vehicle Cre− group. In Cre+ mice, the JZL184-treated group did not have altered freezing during the tone test.