A single corticosterone pretreatment inhibits the hypothalamic-pituitary-adrenal responses to adrenergic and cholinergic stimulation

The purpose of the present study was to determine whether an increased plas ma corticosterone or dexamethasone levels induced by a single corticosteron e or dexamethasone injection to conscious rats affects the hypothalamic-pit uitary-adrenocortical (HPA) activity induced by adrenergic and cholinergic agonists. Male Wistar rats were pretreated subcutaneously (s.c.) with a sin gle dose of dexamethasone (5 mg/kg) or corticosterone (25 mg/kg) 24 or 48 h before intraperitoneal Ii,p.) administration of adrenergic agonists: pheny lephrine, an a-adrenergic receptor agonist, clenbuterol, beta (2)-adrenergi c agonist and noradrenaline acting predominantly on alpha (1)-adrenorecepto rs, and cholinergic agonists: carbachol, a predominant muscarinic receptor agonist and nicotine, a nicotinic receptor agonist. Dexamethasone profoundl y decreased the resting ACTH levels in control rats and given 24 h before e ach of the stimulatory agonist abolished the adrenergic- and cholinergic ag onists-induced ACTH and corticosterone responses. Pretreatment with cortico sterone of control rats did not substantially alter the resting plasma ACTH and serum corticosterone levels measured 24 and 48 h later. A single pretr eatment with corticosterone abolished or powerfully inhibited, perhaps by a feedback mechanism, the ACTH and corticosterone responses induced 24 and 4 8 h later by all adrenergic and cholinergic agonists used in this study. Th ese results indicate that prolonged administration of corticosterone is not necessary to induce almost complete suppression of the HPA responsiveness to adrenergic or cholinergic stimulation. Chronic treatment with corticoste roids to achieve glucocorticoid receptors desensitization does not seem to be required.