Behavioral evidence for beta-adrenoceptor subsensitivity after subacute antidepressant/alpha 2-adrenoceptor antagonist treatment.

The behavioral consequences of beta-adrenoceptor subsensitivity were investigated by determining whether a physiological response that is mediated by beta-receptors, isoproterenol-induced drinking (IID), would be reduced by subacute antidepressant/alpha 2-antagonist treatment. The coadministration of typical (e.g., imipramine) or atypical (e.g., mianserin) antidepressants with yohimbine or piperoxan twice daily for four consecutive days reduced IID. Both the time course as well as the magnitude of beta-adrenoceptor subsensitivity could be behaviorally demonstrated. In addition, the reduction in IID observed after coadministration of imipramine with yohimbine was a centrally mediated effect since it was observed after systemic (subcutaneous) and central (intraventricular) administration of isoproterenol. These results provide evidence that IID is an appropriate behavioral model to demonstrate beta-adrenoceptor subsensitivity following subacute antidepressant/alpha 2-antagonist treatment.