Figure 2: Elevating 2-AG shifts the distribution of stress-susceptibility toward resilience.

(a) Schematic of behavioural paradigm. (b) Histogram of stress-induced change in latency (stress latency minus baseline latency) to consume in the NIH novel-cage test. (c) Gaussian curves fitting the resilient (black) and susceptible (red) subpopulations. Dashed line indicates 120-second post-stress latency increase susceptibility cutoff. (d) Stress-induced change in latency in the whole population and split into susceptible and resilient subgroups. (e) Histogram of pre-stress novel cage latencies categorized by resilience. (f) Individuals’ pre-stress novel-cage latencies. (g) Correlation of resilient subpopulation’s baseline and post-stress changes in latency. (h) Elevated plus maze (EPM) and (i) open-field test (OFT) measured 24 h after foot-shock stress, one week after susceptibility characterization. (j) Histogram of 24 h post-stress changes in latency with JZL-184 treatment 2 h before testing. (k) Gaussian distributions for resilient and susceptible subpopulations with JZL-184 treatment. (l) Stress-induced change in latency in the whole population and split into susceptible and resilient subgroups with JZL-184 treatment. (m) Proportion of susceptible and resilient mice after either vehicle (VEH) or JZL-184 treatment. (n) Correlation between pre-stress latencies and stress-induced changes in latency with JZL-184. Data in a–g was aggregated from 3 cohorts of 40 mice that were used for subsequent experiments (see Methods for details). F and P values for one-way ANOVA shown above (d,f,l). P values shown for pairwise comparisons derived from Sidak multiple comparisons test after ANOVA (d,f,l) or unpaired one-tailed t-test (h,i) shown in each panel. R² and P value for linear regression reported in g,n. P value from chi-squared test reported with susceptibility ratios (m). Data are presented as mean±s.e.m.