5-Hydroxytryptamine receptor function in humans is reduced by acute administration of hydrocortisone

Abstract

5-Hydroxytryptamine_1A (5-HT_1A) receptors have been shown to be suppressed by corticosteroid hormones in a variety of animal experimental paradigms. It has been suggested that this effect may be central to the pathophysiology of severe clinical depressive illness, a condition in which 5-HT_1A receptor function is reduced and corticosteroid hormones are elevated. We report the effects of acute administration of hydrocortisone in normal volunteers on a neuroendocrine model of 5-HT_1A receptor function. Fifteen healthy male volunteers took part in a random order, double blind, placebo controlled study, in which 100 mg hydrocortisone or placebo was administered 11 h before infusion of L-tryptophan (L-TRP). Pre-treatment with hydrocortisone significantly reduced the growth hormone (GH), but not the prolactin (PRL) response to the infusion. These data are consistent with the view that acute administration of corticosteroid hormones significantly impairs 5-HT_1A receptor mediated function in healthy human volunteers and are in line with animal studies of the effects of corticosteroid hormones on 5-HT_1A receptors. We propose that this finding is relevant to the pathophysiological processes which cause severe depressive illness.