Characterization of normal and supersensitive dopamine receptors: Effects of ergot drugs and neuropeptides

Dopamine receptors have been characterized by use of radiolabelled dopamine agonists and antagonists. Using ibotenic acid induced lesions of the striatum, evidence was obtained that 3H-N-propylnorapomorphine (3H-NPA) binding sites and 3H-bromocriptine binding sites are located both on intrastriatal nerve cells and on extrinsic nerve terminals probably mainly originating in the cerebral cortex. Following a 6-hydroxydopamine induced lesion supersensitive dopamine receptors, an increase of binding sites for 3H-NPA and after one year two different binding sites and behavioural supersensitivity have been observed. The dopamine receptor agonists and especially the dopaminergic ergot derivates have been characterized by studying their affinities for 3H-bromocriptine, 3H-spiperone 3H-ADTN and 3H-NPA binding sites in vitro and their effects on the specific in vivo binding of 3H-spiperone and 3H-NPA has been studied. There might exist 3 types of dopamine-receptors. Actions of dopaminergic ergot drugs have been evaluated at supersensitive dopamine receptors. There is a highly preferential action of CF25-397 at these receptors. Prolonged treatment with pergolide can produce a down regulation of normal dopamine receptors by reducing the density of such receptors. Colecystokinin peptides can in vitro reduce the number of 3H-NPA binding sites in the striatum. Thus neuropeptides may represent neuromodulators in the dopamine synapses. (M.J.)