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PACAP-deficient mice show attenuated corticosterone secretion and fail to develop depressive behavior during chronic social defeat stress.
- Source :
-
Psychoneuroendocrinology [Psychoneuroendocrinology] 2013 May; Vol. 38 (5), pp. 702-15. Date of Electronic Publication: 2012 Oct 11. - Publication Year :
- 2013
-
Abstract
- The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) regulates activation of the hypothalamic-pituitary-adrenal (HPA) axis and the adrenal gland in response to various stressors. We previously found that in response to acute psychological stress (restraint), elevated corticotrophin-releasing hormone (CRH) mRNA levels in the hypothalamic paraventricular nucleus (PVN) as well as elevated plasma corticosterone (CORT) were profoundly attenuated in PACAP-deficient mice. To determine whether HPA axis responses and stress-induced depressive-like behaviors in a chronic stress paradigm are affected by PACAP deficiency, we subjected mice to 14 days of social defeat stress. Defeat-exposed PACAP-/- mice showed a marked attenuation of stress-induced increases in serum CORT levels, cellular PVN ΔFosB immunostaining, and depressive-like behaviors (social interaction and forced swim tests) compared to wild-type control mice. The PACAP-/- mice showed reduced PVN FosB-positive cell numbers, but relatively elevated cell counts in several forebrain areas including the medial prefrontal cortex, after social stress. PACAP appears to be specific for mediating HPA activation only in psychological stress because marked elevations in plasma CORT after a systemic stressor (lipopolysaccharide administration) occurred regardless of genotype. We conclude that chronically elevated CORT is a key component of depressive effects of social defeat, and that attenuation of the CORT response at the level of the PVN, as well as extrahypothalamic forebrain regions, in PACAP-deficient mice protects from development of depressive behavior.<br /> (Published by Elsevier Ltd.)
- Subjects :
- Animals
Behavior, Animal physiology
Chronic Disease
Corticosterone blood
Depressive Disorder physiopathology
Hierarchy, Social
Hypothalamo-Hypophyseal System metabolism
Hypothalamo-Hypophyseal System physiology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Pituitary-Adrenal System metabolism
Pituitary-Adrenal System physiology
Stress, Psychological blood
Stress, Psychological metabolism
Stress, Psychological physiopathology
Corticosterone metabolism
Depressive Disorder genetics
Dominance-Subordination
Pituitary Adenylate Cyclase-Activating Polypeptide genetics
Stress, Psychological genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3360
- Volume :
- 38
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Psychoneuroendocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 23062748
- Full Text :
- https://doi.org/10.1016/j.psyneuen.2012.09.006