Vasopressin mediates the response of the combined dexamethasone/CRH test in hyper-anxious rats: implications for pathogenesis of affective disorders.
To investigate the neuroendocrine alterations linked to inborn emotionality in two Wistar rat lines selectively bred for either high (HAB) or low (LAB) anxiety-related behavior, we administered the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test. DEX (12:00 M. (noon); 30 microg/kg) resulted in a significantly less efficient suppression of the diurnal increase in the circulating corticotropin (ACTH) levels in the male HAB rats than in the male LAB rats. In addition, plasma ACTH and corticosterone responses to subsequent CRH (7:30 P.M.; 50 ng/kg) were significantly higher in male HAB rats. The rise in ACTH after CRH in the DEX-pretreated male HAB rats points toward an enhanced activity and involvement of endogenous vasopressin synthesized in the hypothalamic paraventricular nucleus (PVN) and acting at pituitary corticotrope cells. We tested this hypothesis by in situ hybridization and in vivo microdialysis, and found an increase in both basal synthesis and release of vasopressin within the PVN of the male HAB rats. As expected, pretreatment with a selective vasopressin type 1 receptor antagonist abolished the CRH-stimulated increase in ACTH secretion in the DEX-pretreated male HAB rats. The results indicate that vasopressin-mediated effects are critically involved in the profound disturbance of the hypothalamic-pituitary-adrenocortical system in male HAB rats, thus revealing striking parallels to the neuroendocrine situation in human depression.
Keck
Martin E
ME
Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, D-80804, Munich, Germany. keck@mpipsykl.mpg.de
Wigger
Alexandra
A
Welt
Tobias
T
Müller
Marianne B
MB
Gesing
Angela
A
Reul
Johannes M H M
JM
Holsboer
Florian
F
Landgraf
Rainer
R
Neumann
Inga D
ID
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001007:Anxiety / Q000235:genetics / Q000523:psychology*; D001665:Binding Sites; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone; D003907:Dexamethasone; D005246:Feedback / Q000502:physiology; D005938:Glucocorticoids; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D019964:Mood Disorders / Q000503:physiopathology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011863:Radioimmunoassay; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000378:metabolism; D012727:Sex Characteristics; D014667:Vasopressins / Q000502:physiology*
D065092:Antidiuretic Hormone Receptor Antagonists; D005938:Glucocorticoids; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D014667:Vasopressins; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone