Figure 5. 2-AG depletion increases susceptibility to acute stress-induced anxiety-like behaviour.

(a–c) Effects of DO34 (50 mg kg⁻¹; purple) on 2-arachidonoylglycerol (2-AG), arachidonic acid (AA), and anandamide (AEA) in the prefrontal cortex (PFC), amygdala (AMY), nucleus accumbens (NAc), and ventral hippocampus (vHIP). (d) Home cage training (blue lines) and novel cage (NC) latencies and (e) consumption before (NC-V) and after (NC-FS-V) foot-shock stress with vehicle (V) or DO34 treatment. (f) Resilient and (g) susceptible subgroup latencies separated from d. (h) Effects of DO34 on feeding latency relative to vehicle treatment in resilient (black) and susceptible (red) mice. (i) Stress-susceptibility ratios for the same cohort of mice across two weeks after vehicle or DO34 treatment. (j) Resilient population correlations between novel cage test feeding latency and consumption with vehicle and DO34 treatment. (k) Elevated plus maze 24 h after stress exposure with resilient individuals treated with vehicle (VEH) or DO34 (purple) one week after susceptibility categorization. Blue arrows indicate foot-shock stress exposure. F and P values for one-way (d–g) or two-way (a–c) ANOVA shown above individual panels. P values for pairwise comparisons derived from Holm-Sidak multiple comparisons test after ANOVA, unpaired two-tailed t-test (k), or paired two-tailed t-test (h) shown in panels. R² and P value for linear regression shown in j. P value from chi-squared test reported in i. Data are presented as mean±s.e.m.