The behavioral phenotype of pituitary adenylate-cyclase activating polypeptide-deficient mice in anxiety and depression tests is accompanied by blunted c-Fos expression in the bed nucleus of the stria terminalis, central projecting Edinger-Westphal nucleu

▶We examined anxiety levels and c-Fos response to acute stress of PACAP deficient mice. ▶PACAP−/− mice show reduced anxiety in marble burying and light-dark box tests. ▶PACAP−/− mice display brain area-specific reduction in magnitude of c-Fos response. ▶The c-Fos response of mutants is abolished in the DR and blunted in BSTov and EWcp. ▶Limbic, hypothalamic as well as brainstem stress centers are modulated by PACAP.