title: Activation of the HPA axis and depression of feeding behavior induced by restraint stress are separately regulated by PACAPergic neurotransmission in the mouse.
abstract: We measured serum CORT elevation in wild-type and PACAP-deficient C57BL/6N male mice after acute (1 h) or prolonged (2-3 h) daily restraint stress for 7 d. The PACAP dependence of CORT elevation was compared to that of stress-induced hypophagia. Daily restraint induced unhabituated peak CORT elevation, and hypophagia/weight loss, of similar magnitude for 1, 2, and 3 h of daily restraint, in wild-type mice. Peak CORT elevation, and hypophagia, were both attenuated in PACAP-deficient mice for 2 and 3 h daily restraint. Hypophagia induced by 1-h daily restraint was also greatly reduced in PACAP-deficient mice, however CORT elevation, both peak and during recovery from stress, was unaffected. Thus, hypothalamic PACAPergic neurotransmission appears to affect CRH gene transcription and peptide production, but not CRH release, in response to psychogenic stress. A single exposure to restraint sufficed to trigger hypophagia over the following 24 h. PACAP deficiency attenuated HPA axis response (CORT elevation) to prolonged (3 h) but not acute (1 h) single-exposure restraint stress, while hypophagia induced by either a single 1 h or a single 3 h restraint were both abolished in PACAP-deficient mice. These results suggest that PACAP's actions to promote suppression of food intake following an episode of psychogenic stress is unrelated to the release of CRH into the portal circulation to activate the pituitary-adrenal axis. Furthermore, demonstration of suppressed food intake after a single 1-h restraint stress provides a convenient assay for investigating the location of the synapses and circuits mediating the effects of PACAP on the behavioral sequelae of psychogenic stress.
authors.affiliation: a Section on Molecular Neuroscience , National Institute of Mental Health , Bethesda , MD , USA.
authors.forename: Sunny Zhihong
authors.initials: SZ
authors.lastname: Jiang
authors.affiliation: a Section on Molecular Neuroscience , National Institute of Mental Health , Bethesda , MD , USA.
authors.forename: Lee E
authors.initials: LE
authors.lastname: Eiden
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood; D005247:Feeding Behavior / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D003345:Corticosterone
keywords: Acute psychogenic stress; HPA axis; chronic psychogenic stress; corticosterone; hypophagia; pituitary adenylate cyclase-activating polypeptide; prolonged psychogenic stress; restraint stress