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

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