The high-affinity non-peptide CRH1 receptor antagonist R121919 attenuates stress-induced alterations in plasma oxytocin, prolactin, and testosterone secretion in rats.
Evidence from basic and clinical research suggests that hyperactivity of central corticotropin-releasing hormone (CRH) circuits contributes to causality and course of affective disorders. Therefore, CRH receptor antagonists have attracted attention as potential therapeutics. We could previously show that the novel high-affinity non-peptide CRH 1 receptor antagonist R121919 significantly inhibits stress-induced corticotropin release and displays anxiolytic effects in rats selectively bred for high anxiety-related behavior. These animals are characterized by their innate hyper-reactivity of the hypothalamic-pituitary-adrenocortical system linked to an increased emotionality and therefore are suitable for the evaluation of CRH 1 receptor antagonists. Here we show that in addition to its effects on anxiety-related behavior and corticotropin secretion, R121919 attenuates the stress-induced release of corticosterone, prolactin, and oxytocin. Moreover, the decrease in plasma testosterone following exposure to stress is abolished by R121919. Our data indicate that antagonism of CRH 1 receptors may prevent stress-associated endocrine alterations.
Keck
M E
ME
Max Planck Institute of Psychiatry, Munich, Germany. keck@mpipsykl.mpg.de
Welt
T
T
Müller
M B
MB
Landgraf
R
R
Holsboer
F
F
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D005106:Exploratory Behavior / Q000187:drug effects; D006728:Hormones / Q000097:blood* / Q000378:metabolism; D008297:Male; D010121:Oxytocin / Q000097:blood / Q000378:metabolism; D011388:Prolactin / Q000097:blood / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D013312:Stress, Physiological / Q000097:blood / Q000188:drug therapy*; D013739:Testosterone / Q000097:blood / Q000378:metabolism; D000099052:CRF Receptor, Type 1
D006728:Hormones; D011743:Pyrimidines; C412383:R 121919; D018019:Receptors, Corticotropin-Releasing Hormone; D013739:Testosterone; D010121:Oxytocin; D000099052:CRF Receptor, Type 1; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D003345:Corticosterone