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.
Cooper
Matthew A
MA
Department of Psychology, University of Tennessee, Knoxville, TN 37996, USA. mcooper@utk.edu
Huhman
Kim L
KL
D000374:Aggression / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001245:Association Learning / Q000187:drug effects / Q000502:physiology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D006224:Cricetinae; D004291:Dominance-Subordination; D025461:Feedback, Physiological; D005938:Glucocorticoids / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D008797:Metyrapone / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D000099052:CRF Receptor, Type 1
D000963:Antimetabolites; C101628:CP 154526; C101531:CRF receptor type 2; D005938:Glucocorticoids; D006727:Hormone Antagonists; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D008797:Metyrapone