High-resolution radioautographic study of dopamine binding sites in the rat neostriatum using 3H-domperidone.

Abstract

The possibility to use the new ligand 3H-domperidone to identify some dopamine binding sites at the ultrastructural level was assessed in the neostriatum after in vivo administration and high-resolution radioautography. Since this ligand does not cross the blood-brain barrier, intracerebral injections were performed, which resulted in a gradient of diffusion of the tracer. According to increasing distances to the injection site, a quantitative study of the radioautographic reaction was realized. An intense and diffuse reaction took place in the vicinity of the injection site in control rats. On the contrary, numerous accumulations of silver grains were observed in the peripheral zone. The statistical analysis of the distribution of the clusters showed that they were more numerous over the contacts between nerve terminals and dendritic spines than expected from a distribution at random; moreover half of these labelled contacts were differentiated in synapses of the asymmetric type. When the animals were pretreated with haloperidol in order to block the dopaminergic binding sites, we found a decrease in the total number of the number of silver grains. A decrease in the number of clusters of silver grains was noted over nerve terminals and synaptic contacts in both peripheral zones while the nonspecific labelling was increased over other structures. We conclude to the possibility of the detection of the dopaminergic binding sites by electron microscopic radioautography. Moreover we confirm the existence of dopaminergic synapses in the neostriatum with this new technique.