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Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Whitson Street, Bristol BS1 3NY, UK¹ Organon Laboratories Limited, Department of Pharmacology, Newhouse, Lanarkshire ML1 5SH, UK² Organon Laboratories Limited, Department of Molecular Pharmacology, Newhouse, Lanarkshire ML1 5SH, UK

(Correspondence should be addressed to F Spiga; Email: f.spiga{at}bristol.ac.uk)

The following authors have potential conflicts of interest: F S and L R H are funded by Organon Laboratories; C P M, F J T and M C are employed by Organon Laboratories; and M G used to be employed by Organon Laboratories.

We investigated the effect of the glucocorticoid receptor (GR) antagonist Org 34850 on fast and delayed inhibition of corticosterone secretion in response to the synthetic glucocorticoid methylprednisolone (MPL). Male rats were implanted with a catheter in the right jugular vein, for blood sampling and MPL administration, and with an s.c. cannula for Org 34850 administration. All experiments were conducted at the diurnal hormonal peak in the late afternoon. Rats were connected to an automated sampling system and blood samples were collected every 5 or 10 min. Org 34850 (10 mg/kg, s.c.) or vehicle (5% mulgofen in saline) was injected at 1630 h; 30 min later, rats received an injection of MPL (500 µg/rat, i.v.) or saline (0.1 ml/rat). We found that an acute administration of MPL rapidly decreased the basal corticosterone secretion and this effect was not prevented by acute pretreatment with Org 34850. However, blockade of GR with Org 34850 prevented delayed inhibition of MPL on corticosterone secretion measured between 4 and 12 h after MPL administration. Our data suggest an involvement of GR in modulating delayed, but not fast, inhibition induced by MPL on basal corticosterone secretion.