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.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000928:Antidepressive Agents; D000242:Cyclic AMP; D009638:Norepinephrine