OX2R is involved in the ACTH response to acute restraint stress (n = 12/group). ACTH levels were evaluated on the first day of restraint stress following vehicle/vehicle versus CNO/ vehicle pretreatment to evaluate orexin neuron activation (A; no significance by ANOVA), vehicle/ vehicle versus vehicle/MK-1064 pretreatment to evaluate the role of endogenous OX2R (B; significant: 2-Way ANOVA, MK-1064: (F(1,63) = 9.3, p = 0.003), CNO/MK-1064 versus CNO/ vehicle pretreatment to assess the effect of exogenous OX2R activity induction (C; significant: 2Way ANOVA, Drug: F(1,71) = 4.6, p = 0.035), or Vehicle/MK-1064 versus CNO/MK-1064 pretreatment to understand the role of orexin-induced mechanisms other than OX2R (D; no significance by ANOVA). *p < 0.05, **p < 0.01.