Adrenergic alpha2C-receptors reside in rat striatal GABAergic projection neurons: comparison of radioligand binding and immunohistochemistry.

We have investigated the distribution of alpha2c-adrenergic receptors in the rat striatum and characterized the striatal neuron types expressing these receptors. Sequential double-labelled immunocytochemistry was performed with a polyclonal antibody against rat alpha2c-adrenoceptors and antibodies against GABA, Calbindin-D28k, parvalbumin and calretinin. The subregional distribution of alpha2c-adrenoceptor binding sites in the striatum was also quantitatively investigated using selective radioligands. Almost all lightly stained striatal GABAergic neurons, with the morphological characteristics of medium-sized spiny projection neurons (94% of GABAergic cells counted), contained alpha2c-adrenoceptor-immunoreactive structures. Intensely labelled GABAergic inteneurons (6%) were devoid of alpha2c-adrenoceptor immunoreactivity. The co-localization of calbindin- and alpha2c-adrenoceptor immunoreactivity in the majority of the cells confirmed the presence of alpha2c-adrenoceptors in the population of medium-sized spiny neurons. Furthermore, the alpha2c-adrenoceptor/calbindin double-labelling disclosed the existence of three neuronal subsets in the matrix compartment of the striatum: a large proportion (83%) of double-labelled neurons, a population of neurons (8%) that exhibited only alpha2c-adrenoceptor immunoreactivity without calbindin immunoreactivity, and a population of neurons (9%) immunoreactive for calbindin, but lacking alpha2c-adrenoceptors. In addition, alpha2c-adrenoceptor immunolabelled neurons were observed in calbindin-free striatal patches. Parvalbumin- and calretinin-positive neurons never displayed alpha2c-adrenoceptor immunoreactivity, confirming that striatal GABAergic interneurons are devoid of alpha2c-adrenoceptors. The present findings indicate that alpha2c-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.