Differential Effects of Acute and Chronic Social Defeat Stress on Hypothalamic-Pituitary-Adrenal Axis Function and Hippocampal Serotonin Release in Mice

• Published in: Journal of neuroendocrinology Vol. 18; no. 5; pp. 330 - 338
• Main Authors: Keeney, A., Jessop, D. S., Harbuz, M. S., Marsden, C. A., Hogg, S., Blackburn-Munro, R. E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2006; Blackwell Science; Wiley Subscription Services, Inc
• Subjects: ACTH; Adrenocorticotropic Hormone - blood; Animals; Arginine Vasopressin - genetics; Arginine Vasopressin - metabolism; AVP; behaviour; Biological and medical sciences; corticosterone; Corticosterone - metabolism; Corticotropin-Releasing Hormone - genetics; Corticotropin-Releasing Hormone - metabolism; CRF; Dominance-Subordination; forced swimming; Fundamental and applied biological sciences. Psychology; Hippocampus - metabolism; Hypothalamo-Hypophyseal System - metabolism; Immobility Response, Tonic - physiology; Male; Mice; Microdialysis; Paraventricular Hypothalamic Nucleus - metabolism; Pituitary-Adrenal System - metabolism; RNA, Messenger - analysis; Serotonin - metabolism; Social Environment; Stress, Psychological - metabolism; Vertebrates: endocrinology; Endocrine gland; Corticosterone; Central nervous system; Corticotropin releasing factor; ACTH; Hypothalamus; Glucocorticoid; Encephalon; Pituitary gland; Swimming; Behavior; Hormone releasing factor; Release; forced swimming; Serotonin; Steroid hormone; Acute; Rodentia; Stress; Hypothalamic hormone; Vertebrata; Chronic; Mammalia; Adrenocorticotropic hormone; Microdialysis; Adenohypophyseal hormone; Mouse; Animal; CRF; Adrenal hormone; Neurotransmitter; behaviour; AVP; Hippocampus
• ISSN: 0953-8194; 1365-2826
• DOI: 10.1111/j.1365-2826.2006.01422.x

Hyperactivity of the hypothalamic‐pituitary‐adrenal (HPA) stress axis and disturbances in serotonin (5‐HT) neurotransmission have been implicated in the pathogenesis of depressive disorder. Repeated social defeat of male NMRI mice has been shown to induce increases in core body temperature and corticosterone, indicative of a state of chronic stress in subordinate animals. The present study further characterised the HPA axis response to social defeat stress, and also examined hippocampal extracellular 5‐HT release during the stress. Exposure to an acute social defeat elicits increases in plasma adrenocorticotrophic hormone and corticosterone levels, peaking at 15 and 30 min, respectively, and enhances corticotrophin‐releasing factor (CRF) mRNA, but not arginine vasopressin (AVP) mRNA within the medial parvocellular division of the hypothalamic paraventricular nucleus. A concomitant increase in hippocampal corticosterone and 5‐HT levels is observed. By contrast, although chronic social defeat is associated with greatly elevated corticosterone levels, the predominant drive appears to be via parvocellular AVP rather than CRF. Furthermore, subordinate animals allowed to recover for 9 days after chronic social defeat display an increase in immobility in the forced swimming model of depression, indicating that animals previously exposed to the homotypic defeat stress are sensitised to the behavioural effects of a novel stressor. These results demonstrate that social defeat induces prolonged activation of the HPA axis and alterations in 5‐HT neurotransmission that could be of relevance to some of the pathological abnormalities observed in clinical depression.