Blockade of the V(1b) receptor reduces ACTH, but not corticosterone secretion induced by stress without affecting basal hypothalamic-pituitary-adrenal axis activity.
Vasopressin (AVP), produced in parvocellular neurons of the hypothalamic paraventricular nucleus, regulates, together with CRH, pituitary ACTH secretion. The pituitary actions of AVP are mediated through the G protein receptor V(1b) (V(1b)|R). In man, hyperactivity of the hypothalamic-pituitary-adrenal axis has been associated with depression and other stress-related conditions. There are also clinical data suggesting a role for AVP in the dysfunctional HPA axis described in some depressed patients. In this study, we have investigated the effect of a recently synthesised selective antagonist of the V(1b)R both on exogenous AVP-induced ACTH and corticosterone secretion, and on basal and stress-induced pituitary-adrenal activity. Adult male Sprague-Dawley rats treated with the V(1b)R antagonist (Org, 30 mg/kg, s.c.) or vehicle (5% mulgofen in 0.9% saline, 2 ml/kg, s.c.). We found that blockade of the V(1b)R reduced the increase in both ACTH and corticosterone secretion induced by AVP (100 ng, i.v.). The same treatment had no effect either on basal ACTH and corticosterone levels or on the ultradian or diurnal rhythms of corticosterone secretion. Acute administration of the V(1b)R antagonist reduced ACTH secretion following both restraint and lipopolysaccharide, but did not antagonise the ACTH response to noise. The same treatment did not reduce corticosterone secretion in response to any of the three stressors used in this study. Our results confirm that this compound is an antagonist of the V(1b)R in the rat, and that its ability to reduce stress-induced ACTH responses is stressor dependent with differential modulation of pituitary and adrenal responses.
Spiga
Francesca
F
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK. f.spiga@bristol.ac.uk
Harrison
Louise R
LR
Wood
Susan
S
Knight
David M
DM
MacSweeney
Cliona P
CP
Thomson
Fiona
F
Craighead
Mark
M
Lightman
Stafford L
SL
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008297:Male; D009622:Noise; D010913:Pituitary-Adrenal System / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013312:Stress, Physiological
D065092:Antidiuretic Hormone Receptor Antagonists; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone