Antidepressant administration has a differential effect on rat brain alpha 2-adrenoceptor sensitivity to agonists and antagonists.

The aim of this study was to characterize the action of antidepressants on rat brain alpha 2-adrenoceptor function by examining their effect on the yohimbine-sensitive component of the cAMP response to adrenoceptor agonists. Using a prelabeling technique for measuring cAMP accumulation, it was found that chronic (2 weeks) administration of antidepressants increased the potency of yohimbine, an alpha 2-adrenoceptor antagonist, to inhibit norepinephrine-stimulated cAMP accumulation in rat brain cerebral cortical slices. In contrast, antidepressant treatment decreased the ability of the alpha-adrenoceptor agonist 6-fluoronorepinephrine to augment isoproterenol-stimulated cAMP accumulation. The results suggest that antidepressants alter rat brain alpha 2-adrenergic function by shifting the receptor to antagonist-preferring state. Such an effect may contribute to the change in noradrenoceptor responsiveness that is characteristic of antidepressant administration.