Adrenal corticoids regulate sensitivity of noradrenaline receptor-coupled adenylate cyclase in brain.

Abstract

Considerable evidence indicates that alterations in the availability of noradrenaline (NA) at postsynaptic sites can cause compensatory changes in the NA stimulated cyclic AMP generating system in various brain regions. Thus, an increased responsiveness to NA has been reported in the limbic forebrain and cortex following reserpine or 6-hydroxydopamine1–3. Conversely, manipulations which increase the availability of NA at receptor sites (monoamine oxidase (MAO) inhibitors, electroconvulsive treatment (ECT), tricyclic antidepressants) cause a decrease in responsiveness4–6. This up and down-regulation of central noradrenergic sensitivity is generally linked to changes of the density of β-adrenergic receptors7–10. The findings that psychotropic drugs which can either precipitate (reserpine) or alleviate (tricyclic antidepressants, MAO inhibitors and also ECT) depressive states cause opposite changes in the NA receptor-coupled adenylate cyclase system in brain have provided the basis for a revised catecholamine hypothesis of affective disorders11. It has also been suggested that the pituitary adrenal axis may have a role in mood disorders12. Since manipulation of the levels of corticosterone through bilateral adrenalectomy can alter the sensitivity of catecholamine-sensitive adenylate cyclase systems in preparations from liver13,14 and adipose tissue15, we have tried to determine if corticosterone could regulate the NA receptor-coupled adenylate cyclase system in brain tissue. We now report that adrenal corticoids can alter the sensitivity of this system to NA.