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.
Flügge
G
G
German Primate Centre, Göttingen, Germany. gflugge@www.dpz.gwdg.de
D000311:Adrenal Glands / Q000187:drug effects; D000818:Animals; D001345:Autoradiography; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D006854:Hydrocortisone / Q000494:pharmacology* / Q000652:urine; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D008024:Ligands; D008297:Male; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D013315:Stress, Psychological / Q000503:physiopathology*; D014418:Tupaiidae / Q000523:psychology*
D008024:Ligands; D018341:Receptors, Adrenergic, alpha-2; C058525:2-methoxyidazoxan; D006854:Hydrocortisone; D019329:Idazoxan