Effect of paroxetine, a selective 5-hydroxytryptamine uptake inhibitor, on beta-adrenoceptors in rat brain: autoradiographic and functional studies.

Quantitative receptor autoradiography was used to investigate the effects of paroxetine (8.3 mg/kg), amitriptyline (26 mg/kg) and desipramine (17 mg/kg), administered daily in the drinking water for 21 days, on the number of beta 1- and beta 2-adrenoceptors in the cortex of the rat. In addition, the effect of these drugs on the function of beta-adrenoceptors was examined by measuring noradrenaline- and isoprenaline-stimulated production of cyclic AMP in slices of cortex. Paroxetine did not alter the number of cortical beta 1 or beta 2-adrenoceptors nor did it induce any functional changes in beta-adrenoceptor-linked adenylyl cyclase. In contrast, desipramine caused a significant reduction in the density of beta 1-adrenoceptors and in the sensitivity of both noradrenaline and isoprenaline-stimulated adenylyl cyclase. Although amitriptyline significantly reduced the number of beta 1-adrenoceptors in cortical membranes, no such changes could be detected by autoradiography. It is apparent from these and other studies, that the ability of antidepressants to down-regulate central beta-adrenoceptors is not a property shared by all antidepressants. In particular, the more potent and selective inhibitors of the uptake of 5-HT, such as paroxetine, appear to be devoid of effects on this receptor system.