OPPOSITE EFFECTS ON HIPPOCAMPAL CORTICOSTEROID RECEPTORS INDUCED BY STIMULATION OF BETA-NORADRENERGIC AND ALPHA-1-NORADRENERGIC RECEPTORS

Central corticosteroid receptors play an important role in the regulation of the secretion of corticosterone. Although these receptors are thought to be regulated by circulating levels of corticosterone, there is evidence for direct neural control. For example, it has been shown that noradrenergic lesions can both increase and decrease corticosteroid receptors depending on the brain structure involved. In the present study, we investigated the role of different noradrenergic receptors in the rat, by examining the effect of the acute administration of agonists and antagonists of beta and alpha(1) noradrenergic receptors on hippocampal type I and type II corticosteroid receptor levels. The effects of these drugs were studied in adrenalectomized animals whose plasma levels of corticosterone were maintained in the physiological range by implantation of corticosterone pellets. Our results show that the beta receptor agonist salbutamol (5 mg/kg) increased the number of type I and type II hippocampal corticosteroid receptors. This effect was blocked by the beta receptor antagonist propranolol (5 mg/kg), which had no effect on its own. In contrast, the alpha(1) receptor agonist phenylephrine (100 mu g) reduced the number of type I and type II corticosteroid receptors, whereas the alpha(1) receptor antagonist prazosin (0.5 mg/kg) increased type I receptors. The effect of prazosin was attributed to an increase in the relative beta tonus resulting from blockade of alpha(1) receptors. Its effect was reversed by the simultaneous injection of the beta receptor antagonist propranolol. In conclusion, our results show that noradrenergic transmission can have both a facilitatory and an inhibitory action on central corticosteroid receptors by acting respectively on beta and alpha(1) noradrenergic receptors. Since noradrenergic neurons and the hypothalamo-pituitary-adrenal axis are known to be involved in various psychopathological conditions, these results may be relevant to treatment for dysregulation of corticosterone secretion.