Blockade of the V1b receptor reduces ACTH, but not corticosterone secretion induced by stress without affecting basal hypothalamic-pituitary-adrenal axis activity

Spiga, F., Harrison, L.R., Wood, S., Knight, D.M., MacSweeney, C.P., Thomson, F. , Craighead, M. and Lightman, S.L. (2009) Blockade of the V1b receptor reduces ACTH, but not corticosterone secretion induced by stress without affecting basal hypothalamic-pituitary-adrenal axis activity. Journal of Endocrinology, 200(3), pp. 273-283. (doi: 10.1677/JOE-08-0421)

Abstract

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 V1b (V1b|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 V1bR 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 V1bR 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 V1bR 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 V1bR 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 V1bR in the rat, and that its ability to reduce stress-induced ACTH responses is stressor dependent with differential modulation of pituitary and adrenal responses.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Thomson, Dr Fiona
• Authors: Spiga, F., Harrison, L.R., Wood, S., Knight, D.M., MacSweeney, C.P., Thomson, F., Craighead, M., and Lightman, S.L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Endocrinology
• Publisher: BioScientifica
• ISSN: 0022-0795
• ISSN (Online): 1479-6805
• Published Online: 13 November 2008