Receptor dynamics: effect of repeated administration of desmethylimipramine on the noradrenergic systems in rat brain

The effects of a single and of repeated administration of desmethylimipramine (DMI) on the densities of various receptors and on the metabolism of noradrenaline (NA) were determined in rat brain. Inhibition of the uptake of NA into cortex slices, measured in vitro, was not diminished after repeated administration of DMI. The turnover of NA was inhibited only after the single administration of the drug. After repeated administration the turnover of NA was again within the normal range, but now the density of beta-receptors was significantly reduced. Repeated administration of DMI had no significant effect on the densities of alpha-adrenergic, dopaminergic, cholinergic, histaminergic, opiate and serotoninergic receptors. These results indicate that the continued blockade of NA-reuptake caused a selective desensitization of beta-receptor-regulated systems in the brain.