Adrenergic alpha(2C)-receptors reside in rat striatal gabaergic projectionneurons: Comparison of radioligand binding and immunohistochemistry

We have investigated the distribution of alpha(2C)-adrenergic receptors in the rat striatum and characterized the striatal neuron types expressing the se receptors. Sequential double-labelled immunocytochemistry was performed with a polyclonal antibody against rat alpha(2C)-adrenoceptors and antibodi es against GABA, Calbindin-D-28k, parvalbumin and calretinin. The subregion al distribution of alpha(2C)-adrenoceptor binding sites in the striatum was also quantitatively investigated using selective radioligands. Almost all lightly stained striatal GABAergic neurons, with the morphological characte ristics of medium-sized spiny projection neurons (94% of GABAergic cells co unted), contained alpha(2C)-adrenoceptor-immunoreactive structures. Intense ly labelled GABAergic interneurons (6%) were devoid of alpha(2C)-adrenocept or immunoreactivity. The co-localization of calbindin- and alpha(2C)-adreno ceptor immunoreactivity in the majority of the cells confirmed the presence of alpha(2C)-adrenoceptors in the population of medium-sized spiny neurons . Furthermore, the alpha(2C)-adrenoceptor/calbindin double-labelling disclo sed the existence of three neuronal subsets in the matrix compartment of th e striatum: a large proportion (83%) of double-labelled neurons, a populati on of neurons (8%) that exhibited only alpha(2C)-adrenoceptor immunoreactiv ity without calbindin immunoreactivity, and a population of neurons (9%) im munoreactive for calbindin, but lacking alpha(2C)-adrenoceptors. In additio n, alpha(2C)-adrenoceptor immunolabelled neurons were observed in calbindin -free striatal patches. Parvalbumin- and calretinin-positive neurons never displayed alpha(2C)-adrenoceptor immunoreactivity, confirming that striatal GABAergic interneurons are devoid of alpha(2C)-adrenoceptors. The present findings indicate that alpha(2C)-adrenoceptors are localized in GABAergic medium-sized spiny projection neurons but not in interneurons of the rat striatum, and that they may modulate both the direct and indirect pathways of the basal ganglia, as well as participate in the regulation of mesencephalic dopaminergic neurons. (C) 1999 IBRO. Published by Elsevier Sc ience Ltd.