ADCYAP1 and major depressive disorder: We decided to use these heterozygous (HZ) mice because they exhibited reduced PACAP levels in the brain [7] associated with a depression-like phenotype [8], and the role of PACAP has been shown in multiple aspects of stress adaptation response, including the activity of higher-order limbic centers [8,9] and the regulation of the hypothalamus–pituitary–adrenal (HPA) axis [6,8,9,10,11,12,13,14,15,16,17,18,19,20].