n=8 for all panels. EU-EU: mice with access to water for the entire study. DE-EU: mice that were dehydrated overnight then restored water just after treatment with VEH or CNO. DE-DE: mice that were dehydrated overnight and after treatment with VEH or CNO. (A) Dehydration-induced drinking 5 hours after i.p. injection of VEH or CNO in overnight dehydrated (DE) mice upon restoration of water (DE-EU mice). ***p=0.0005. (B) Body weight change 5 hours after i.p. injection of VEH or CNO. 2-way RM-ANOVA (2×3) for interaction of hydration status and njection condition, F (2, 14) = 1.171, p=0.3387. Hydration status: F (2, 14) = 15.58, p=0.0003. Dunnett’s multiple comparisons test for the difference between EU-EU (CNO) and DE-EU (CNO), p=0.0764. Injection condition: F (1, 7) = 2.112, p=0.1894 (C) Total food intake 5 hours after i.p. injection of VEH or CNO in overnight dehydrated. Dunnett’s multiple comparisons test for the difference between EU-EU (CNO) and DE-EU (CNO), p=0.0359. Sidak`s multiple comparisons test for the difference between DE-EU (VEH) and DE-EU (CNO), p=0.0018. 2-way RM-ANOVA (2×3) for interaction of hydration status and injection condition, F (2, 12) = 1.414, p=0.2809. Injection condition: F (1, 6) = 4.13, p=0.0884. Hydration status: F (2, 12) = 1.989, p=0.1795. “+” indicates significant difference between groups within a treatment and “*” indicates significant difference within the group between different treatments.