Intracerebroventricular administration of corticotrophin-releasing hormone receptor antagonists produces different effects on hypothalamic pituitary adrenal responses to novel restraint depending on the stress history of the animal.
Corticotrophin-releasing hormone (CRH) regulates acute stress-induced changes in neuroendocrine function and behaviour. However, little is known about CRH functions in animals that have prior experience with repeated stress. Repeatedly-stressed rats exhibit a habituated hypothalamic-pituitary-adrenal (HPA) response to a familiar, homotypic stressor but exhibit maintained or enhanced HPA responses to a novel, heterotypic stressor. We examined the effects of intracerebroventricular (i.c.v.) administration of two different nonselective CRH receptor antagonists, alpha-helical CRH(9-41) (ahCRH) or D-Phe CRH(12-41) (D-PheCRH), on HPA responses to acute restraint in rats previously exposed to repeated cold stress (i.e. facilitated responses). Antagonists were administered as single i.c.v. injections prior to restraint to provide a general index of CRH function in control versus repeatedly-stressed rats. CRH receptor blockade with either ahCRH or D-PheCRH produced different effects on HPA responses to novel restraint depending on whether the animal had been previously cold stressed or not. Interestingly, some agonist-type effects were observed but only in repeatedly-stressed rats. In summary, these results indicate that manipulations of the CRH receptor have different effects on HPA activity depending on the stress history of the animal.
Vining
C
C
Department of Anesthesiology, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Iyer
V
V
Bhatnagar
S
S
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism*; D011214:Practice, Psychological; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism*
D006727:Hormone Antagonists; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; C113202:phenylalanyl corticotropin-releasing factor (12-41); D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41); D003345:Corticosterone