title: Impact of PACAP and PAC1 receptor deficiency on the neurochemical and behavioral effects of acute and chronic restraint stress in male C57BL/6 mice.
abstract: Acute restraint stress (ARS) for 3 h causes corticosterone (CORT) elevation in venous blood, which is accompanied by Fos up-regulation in the paraventricular nucleus (PVN) of male C57BL/6 mice. CORT elevation by ARS is attenuated in PACAP-deficient mice, but unaffected in PAC1-deficient mice. Correspondingly, Fos up-regulation by ARS is greatly attenuated in PACAP-deficient mice, but much less so in PAC1-deficient animals. We noted that both PACAP- and PAC1-deficiency greatly attenuate CORT elevation after ARS when CORT measurements are performed on trunk blood following euthanasia by abrupt cervical separation: this latter observation is of critical importance in assessing the role of PACAP neurotransmission in ARS, based on previous reports in which serum CORT was sampled from trunk blood. Seven days of chronic restraint stress (CRS) induces non-habituating CORT elevation, and weight loss consequent to hypophagia, in wild-type male C57BL/6 mice. Both CORT elevation and weight loss following 7-day CRS are severely blunted in PACAP-deficient mice, but only slightly in PAC1-deficient mice. However, longer periods of daily restraint (14-21 days) resulted in sustained weight loss and elevated CORT in wild-type mice, and these effects of long-term chronic stress were attenuated or abolished in both PACAP- and PAC1-deficient mice. We conclude that while a PACAP receptor in addition to PAC1 may mediate some of the PACAP-dependent central effects of ARS and short-term (<7 days) CRS on the hypothalamo-pituitary-adrenal (HPA) axis, the PAC1 receptor plays a prominent role in mediating PACAP-dependent HPA axis activation, and hypophagia, during long-term (>7 days) CRS.
authors: a Section on Molecular Neuroscience and.
authors: Tomris
authors: T
authors: Mustafa
authors: a Section on Molecular Neuroscience and.
authors: Sunny Zhihong
authors: SZ
authors: Jiang
authors: b Section on Functional Neuroanatomy, National Institute of Mental Health , Bethesda , MD USA , and.
authors: Adrian M
authors: AM
authors: Eiden
authors: c Institute of Anatomy, Philipps University , Marburg , Germany.
authors: Eberhard
authors: E
authors: Weihe
authors: a Section on Molecular Neuroscience and.
authors: Ian
authors: I
authors: Thistlethwaite
authors: a Section on Molecular Neuroscience and.
authors: Lee E
authors: LE
authors: Eiden
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000172:deficiency / Q000235:genetics*; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000172:deficiency / Q000235:genetics*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C495402:Adcyap1 protein, mouse; C495504:Adcyap1r1 protein, mouse; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016760:Proto-Oncogene Proteins c-fos; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D003345:Corticosterone
keywords: Acute psychogenic stress; HPA axis; PAC1 receptor; chronic psychogenic stress; pituitary adenylate cyclase-activating polypeptide; restraint