Regulation and function of noradrenaline receptor systems in brain: Psychopharmacological aspects

Abstract

Central β-adrenoceptors are coupled to adenylate cyclase in a stimulatory manner. However, there is only circumstantial evidence that α 2-adrenoceptors in brain are coupled to adenylate cyclase in an inhibitory manner. The desensitization of the β-adrenoceptor system induced by antidepressants seems to be a common action of clinically effective antidepressants. α 2-Adrenoceptor subsensitivity, if it occurs following administration of some antidepressants, contributes to the development of down-regulation of β-adrenoceptors. The occupancy of adrenoceptors by noradrenaline (NA) is a prerequisite for both desensitization of the system and the reduction in the number of β-adrenoceptors while serotonin (5-HT) is co-required with NA for the regulation of the density of β-adrenoceptors. The decrease in the number of β-adrenoceptors induced by antidepressants is rapidly reversible following inhibition of 5-HT synthesis by p-chlorophenylalanine. Since β-adrenoceptor-coupled adenylate cyclase systems function as kinetic amplification systems, small changes in the NA signal transfer are amplified or deamplified respectively. (β-Adrenoceptors may also subserve a critical role in neuronal membranes by determining the sensitivity of other membrane receptor systems.