Effects of cortisol on brain alpha2-adrenoceptors: potential role in stress

It has been proposed that behavioural changes induced by chronic psychosocial stress in male tree shrews might be related to alterations in the central nervous alpha2-adrenoceptor system. In the noradrenergic centres of the brain, alpha2-adrenoceptors function as autoreceptors regulating noradrenaline release. Chronic stress downregulates these receptors in several brain regions. Since during stress, the activity of the hypothalamus-pituitary-adrenal axis is increased leading to high concentrations of plasma glucocorticoids, we investigated whether the effects of chronic stress can be mimicked by cortisol treatments. Two experiments were performed: a short-term treatment (males were injected i.v. with 1.5 mg cortisol and brains were dissected 2 h later) and a long-term treatment (animals received the hormone in their drinking water for 5 days; daily uptake 3-7 mg). The short-term treatment (injection), similar to the stress effects, downregulated alpha2-adrenoceptors in several brain regions. In contrast, the long-term oral treatment induced regional receptor upregulation. These data show: (i) that glucocorticoids regulate alpha2-adrenoceptors in the brain; (ii) that the duration and/or the route of cortisol application determines the results: and (iii) that chronic stress effects are not only due to the long-term glucocorticoid exposure, but also to other elements of the stress response.