Blocking corticotropin-releasing factor-2 receptors, but not corticotropin-releasing factor-1 receptors or glucocorticoid feedback, disrupts the development of conditioned defeat

Several neuroendocrine signals of the hypothalamic-pituitary adrenal (HPA) axis are released following exposure to stressful events It has long been proposed that the signals in this cascade each act to modify ongoing and future behavior In this study we investigated whether blocking glucocorticoid synthesis corticotropin-releasing factor (CRF)-1 receptors or CRF 2 receptors during social defeat would alter subsequent behavioral responses We used a conditioned defeat model in Syrian hamsters in which social defeat results in a dramatic shift from territorial aggression to increased submissive and defensive behavior in future social encounters We found that intracerebroventricular administration of anti-sauvagine-30 a CRF-2 receptor antagonist prior to social defeat training reduced the acquisition of conditioned defeat In contrast the acquisition of conditioned defeat was not altered by the CRF-1 receptor antagonist CP-154 526 or the glucocorticoid synthesis inhibitor metyrapone Our results suggest that CRF and perhaps related neuropeptides such as urocortins act at CRF-2 receptors to promote the development of defeat-induced changes in social behavior whereas signaling at CRF-1 and glucocorticoid receptors plays a negligible role in this process (C) 2010 Elsevier Inc All rights reserved