Quantitative autoradiography of ³H-nomifensine binding sites in rat brain

The distribution of ³H-nomifensine binding sites in the rat brain has been studied by quantitative autoradiography. The binding of ³H-nomifensine to caudate putamen sections was saturable, specific, of a high affinity (kd = 56 nM) and sodium-dependent. The dopamine uptake inhibitors benztropine, nomifensine, cocaine, bupropion and amfonelic acid were the most potent competitors of ³H-nomifensine binding to striatal sections. The highest levels of (benztropine-displaceable) ³H-nomifensine binding sites were found in the caudateputamen, the olfactory tubercle and the nucleus accubenss. 6-Hydroxydopamine-induced lesion of the ascending dopaminergic bundle resulted in a marked decrease in the ³H-ligand binding in these areas. Moderately high concentrations of the ³H-ligand were observed in the bed nucleus of the stria terminalis, the anteroventral thalamic nucleus, the cingulate cortex, the lateral septum, the hippocampus, the amygdala, the zona incerta and some hypothalamic nuclei. There were low levels of binding sites in the habenula, the dorsolateral geniculate body, the substantia nigra, the ventral tegmental area and the periaqueductal gray matter. These autoradiographic data are consistent with the hypothesis that ³H-nomifensine binds primarily to the presynaptic uptake site for dopamine but also labels the norepinephrine uptake site.