INFLUENCE OF 6-OHDA LESION OF CENTRAL NORADRENERGIC SYSTEMS ON CORTICOSTEROID RECEPTORS AND NEUROENDOCRINE RESPONSES TO STRESS

Two types of receptor for adrenocortical hormones (type I or mineralocorticoid and type II or glucocorticoid) in the hippocampus and hypothalamus mediate the effects of corticosteroids on various brain functions including the negative feedback control of hypothalamo-pituitary-adrenal (HPA) axis activity. These brain regions are also densely innervated by noradrenergic terminals which may play a role in the regulation of HPA axis activity and the feedback action of corticosteroids. However, direct evidence for a noradrenergic control of corticosterone receptors is lacking. The present experiments tested the effects of 6-hydroxydopamine lesion of noradrenergic ascending pathways at the level of the pedunculus cerebellaris superior (PCS) on the status of type I and type II corticosteroid receptors. Binding of [3H]corticosterone was evaluated in cytosolic fractions of 24-h adrenalectomized animals 3 weeks after surgery. The PCS lesion produced an up-regulation of type I corticosteroid receptors in the hippocampus and of the type II receptor in the hypothalamus. The number of these receptors (Bmax) increased without any change in their affinityfor corticosterone (Kd). Furthermore, in a functional study, we tested the effects of the lesion on the neuroendocrine responses to stress. Plasma corticosterone levels were lower in lesioned rats both under basal conditions and in response to the stress of gentle handling or exposure to footshock, indicating reduced activity of the HPA axis. These results are in line with recent studies indicating a facilitatory function of noradrenergic pathways on the HPA axis and suggest that this action could be mediated via a modulation of corticosteroid receptors. Although basal circulating catecholamine levels were not altered by the lesion, the noradrenaline response to footshock stress was increased. This result is consistent with the demonstrated tonic inhibition of the sympatho-adrenomedullary system by corticosteroids. These data provide further evidence for the close relationship between catecholaminergic systems and corticosteroids. © 1990.