The responsiveness of cerebral cortical adrenergic receptors after chronic administration of atypical antidepressant mianserin

Abstract

The aim of this study was to evaluate the effect of mianserin, a second generation tetracyclic antidepressant agent, on the receptors' and second messenger systems related to noradrenergic transmission in the cerebral cortex of the rat. In in vitro experiments we confirmed that mianserin binds with equal potency to alpha 1- and alpha 2-adrenoceptors and does not affect beta 1-adrenoceptors. It inhibited the noradrenaline-stimulated inositol phosphate accumulation and did not change the cyclic AMP responses to noradrenaline and isoproterenol. The drug attenuated the inhibitory action of PKC activator, TPA, on the noradrenergic response from alpha 1-adrenoceptor and the potentiating action of TPA on the cyclic AMP stimulated with noradrenaline and isoproterenol. In chronic experiments we have found that, in contrast to most antidepressants, chronic treatment with mianserin does not produce strong beta-downregulation, but increases the maximal inositol phosphate response from alpha 1-adrenoceptor. The results indicate that alpha 1-upregulation might be a characteristic of those efficient antidepressant drugs which do not produce a strong beta-downregulatory effect.