Fig. 3—

Results from icv Orx₂ agonist and antagonist experiments (Staton et al., 2018) that activation of Orx₂ receptors is anxiolytic and anti-depressive. Behavioral phenotypes derived from social interaction in the Stress-Alternatives Model (SAM) differed, Stay (clear bar) vs Escape (hatched bar; statistical significance between behavioral phenotypes is represented by differing Roman letters atop the bar, such that A is different from B), with more anxious behavior evident in Stay mice by increased A) Mean (± SEM) freezing (t₁₃ = 2.7, P ≤ 0.018) in response to fear conditioning ([Freezing after CS/Freezing before] × 100); B) Freezing during SAM social aggression (% time freezing; t₁₆ = 2.4, P ≤ 0.03); and C) Startle responses (/min; t₁₄ = 2.7, P ≤ 0.019); but enhanced anxiolytic responses in Escape phenotype mice by increased D) Mean (± SEM) % Time attentive to the hole (t₁₆ = 4.67, P ≤ 0.001), and E) Resilience score in the Social Interaction Preference test (SIP; t₁₈ = 3.82, P < 0.001), but F) did not affect locomotion. Activation of the Orx₂ receptor by Ala¹⁵, D-Leu¹¹-Orx_B (light gray bars) reduces A) Freezing during fear conditioning in Stay mice (F_2,31 = 4.86, P ≤ 0.015; statistical significance between Stay groups is represented by differing Greek letters atop the bar, such that α is different from β), B) Conflict induced freezing (F_2,25 = 4.8, P < 0.017), and C) Startle responses (F_2,21 = 3.89, P ≤ 0.036), but increases D) % Time attentive to the hole (F_2,24 =12.37, P < 0.001), which may promote an 11% increase in escape behavior, and E) SIP resilience score “(time near container with a social target / time near a novel container lacking a social target × 100; such that a score < 100 indicates susceptibility, and a score > 100 indicates resilience) in Stay mice (F_2,30 = 4.6, P ≤ 0.018; comparing Escape mice: t₁₁ = 2.6, P ≤ 0.025). Inhibition of the Orx₂ receptor by MK-1064 (dark gray bars) in Stay mice increases B) Conflict freezing on injection day compared to day 2, and plasma corticosterone (data not shown). In Escape phenotype mice the Orx₂ antagonist (dark gray hatched bar) increases E) Susceptibility score in SIP test (statistical significance between Escape groups is represented by differing Italic letters atop the bar, such that Y is different from Z), and reduces the number of escaping mice by half (data not shown), but F) did not affect locomotion (F_2,35 = 0.39, P ≥ 0.68).