title: PACAP centrally mediates emotional stress-induced corticosterone responses in mice.
abstract: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide widely distributed in the nervous system. Recently, PACAP was shown to be involved in restraint stress-induced corticosterone release and concomitant expression of the genes involved in hypothalamic-pituitary-adrenal (HPA) axis activation. Therefore, in this study, we have addressed the types of stressors and the levels of the HPA axis in which PACAP signaling is involved using mice lacking PACAP (PACAP⁻/⁻). Among four different types of stressors, open-field exposure, cold exposure, ether inhalation, and restraint, the corticosterone response to open-field exposure and restraint, which are categorized as emotional stressors, but not the other two, was markedly attenuated in PACAP⁻/⁻ mice. Peripheral administration of corticotropin releasing factor (CRF) or adrenocorticotropic hormone induced corticosterone increase similarly in PACAP⁻/⁻ and wild-type mice. In addition, the restraint stress-induced c-Fos expression was significantly decreased in the paraventricular nucleus (PVN) and medial amygdala (MeA), but not the medial prefrontal cortex, in PACAP⁻/⁻ mice. In the PVN of PACAP⁻/⁻ mice, the stress-induced c-Fos expression was blunted in the CRF neurons. These results suggest that PACAP is critically involved in activation of the MeA and PVN CRF neurons to centrally regulate the HPA axis response to emotional stressors.
authors: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Naohiro
authors: N
authors: Tsukiyama
authors: Yoko
authors: Y
authors: Saida
authors: Michiya
authors: M
authors: Kakuda
authors: Norihito
authors: N
authors: Shintani
authors: Atsuko
authors: A
authors: Hayata
authors: Yoshiko
authors: Y
authors: Morita
authors: Mamoru
authors: M
authors: Tanida
authors: Minako
authors: M
authors: Tajiri
authors: Keisuke
authors: K
authors: Hazama
authors: Katsuya
authors: K
authors: Ogata
authors: Hitoshi
authors: H
authors: Hashimoto
authors: Akemichi
authors: A
authors: Baba
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000679:Amygdala / Q000502:physiology; D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone; D051379:Mice; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000172:deficiency / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012149:Restraint, Physical / Q000502:physiology; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016760:Proto-Oncogene Proteins c-fos; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone