MC4R and Anxiety: However, several studies suggest that the activation of MC3/4R is anxiogenic, while blockade reduces anxiety.70, 71, 72 For instance, antagonism of MC4Rs, either subcutaneously or orally, reduced anxiety under baseline conditions, following exposure to swim stress.73 Similarly, intranasal application of the MC4R antagonist HS014 decreased anxiety‐like behaviors following single prolonged stress.74 Since an important control, with intranasally applied MC4R antagonist but without stress exposure, was missing, the behavioral effects of HS014 treatment alone are not entirely clear.