Enhancement of the responsiveness of cortical adrenergic receptors by chronic administration of the 5-hydroxytryptamine uptake inhibitor citalopram.

The aim of this study was to evaluate the effect of citalopram, a second generation antidepressant agent producing no beta-down-regulation, on the receptors and second messenger systems related to noradrenergic transmission in the cerebral cortex of the rat. We confirmed that citalopram does not bind to alpha 1-, alpha 2-, and beta 1-adrenoceptors, but we found that it attenuates the inhibitory action of the protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate, on the noradrenergic response from alpha 1-adrenoceptor. In contrast to most antidepressants, chronic treatment with citalopram does not produce beta-down-regulation, but increases the responses to noradrenaline from beta-adrenoceptors without increasing the beta 1-adrenoceptor density. Chronic treatment with citalopram also increases the maximal response from alpha 1-adrenoceptor. The results indicate that beta-down-regulation is not a necessary characteristic of an efficient antidepressant drug.