Ultrastructural localization of D1 dopamine receptor immunoreactivity in rat striatonigral neurons and its relation with dopaminergic innervation.

We have investigated by immunohistochemistry the cellular and subcellular distribution of the D1 dopamine receptor (D1R) in the rat striatonigral complex and its relation with the dopaminergic innervation. In the striatum, single pre-embedding immunoperoxidase and immunogold labeling demonstrate that D1R is mainly located on dendritic shafts and spines of spiny dendrites. D1R is also found in association with the plasma membrane of half of the perikarya of medium spiny neurons. Double labeling experiments allowing the simultaneous detection of D1R and of tyrosine hydroxylase (TH) demonstrate that D1R distribution does not match dopamine innervation: a majority of the receptors is located at sites distant from dopamine profiles and there is no significant D1R enrichment at sites of membrane appositions between dopamine and D1R profiles. In the substantia nigra, D1R is located at pre-synaptic sites on small diameter axons which are not in contact with TH-positive elements, and on terminal boutons forming symmetrical synapses on TH-positive or negative dendrites. These data demonstrate abundance and wide distribution of D1R at various extrasynaptic sites in the striatum and the substantia nigra, bringing strong evidence of anatomical basis for dopamine non-synaptic volume transmission in the rat striatonigral complex.