MC4R and Anxiety: Similarly to the WT group, the MC4R KO vehicle-treated ELS spent significantly less time in the light zone compared with MC4R KO controls (p = 0.003, GEE); however, ACTH treatment was not able to ameliorate the anxiety (p = 0.005 to the KO control group) indicating a MC4R-dependent mechanism for this amelioration, with a significant genotype–treatment effect (p = 0.000061, GEE).