title: Blockade of pituitary-adrenal axis activation induced by peripheral immunoneutralization of corticotropin-releasing factor does not affect the behavioral response to social defeat stress in rats.
abstract: Specific in vivo immunoneutralization of hypophysiotrophic corticotropin-releasing factor (CRF) and vasopressin (AVP) was used to investigate the respective roles of these circulating peptides in the hormonal response to a social stressor in Wistar rats. The effect of peripheral immunoneutralization on the behavioral response to the same social stressor was also studied. Stress was produced using social defeat in a resident-intruder paradigm, in which an intruder male rat, equipped with an indwelling IV catheter, was confronted with a dominant resident male rat. To minimize the physical component of the agonistic interaction, the intruder was protected immediately after the resident's first attack in a Plexiglas/wire-mesh enclosure. In the following time interval, the resident continued to threaten the protected intruder, which showed a significant increase in plasma immunoreactive adrenocorticotropic hormone (ACTH) and corticosterone levels compared to those measured in rats exposed to a control procedure. The hypothalamo-pituitary-adrenal (HPA) axis response to social defeat stress was totally abolished by pretreatment with an anti-CRF serum (0.3 ml IV) but not an anti-AVP serum (0.75 ml IV). An animal model for anxiety in rodents, the elevated plus-maze, was used to study the emotional response to social defeat stress in rats given anti-CRF serum or normal serum. A significant reduction of open-arm exploration was observed in defeated rats tested 10 min after the end of the agonistic interaction when compared with control animals for all antisera treatment group, indicating an "anxiogenic-like" emotional response to the social defeat stress. Pretreatment with anti-CRF serum did not affect the behavioral performance of defeated and control rats. These results suggest that: 1) social defeat stress produced an activation of the HPA axis in the rat which is mediated by hypophysiotrophic CRF but not AVP; and 2) the peripheral activation of the HPA axis induced by social defeat stress is not involved in the behavioral response to stress as measured in the elevated plus-maze.
authors.affiliation: Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
authors.forename: E M
authors.initials: EM
authors.lastname: Pich
authors.forename: S C
authors.initials: SC
authors.lastname: Heinrichs
authors.forename: C
authors.initials: C
authors.lastname: Rivier
authors.forename: K A
authors.initials: KA
authors.lastname: Miczek
authors.forename: D A
authors.initials: DA
authors.lastname: Fisher
authors.forename: G F
authors.initials: GF
authors.lastname: Koob
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001127:Arginine Vasopressin / Q000502:physiology; D001143:Arousal / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D004193:Discrimination Learning / Q000502:physiology; D004291:Dominance-Subordination; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009949:Orientation / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011340:Problem Solving / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012931:Social Environment
chemical_list: D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone