Quantitative autoradiography of dopamine D2 sites in rat caudate-putamen: Localization to intrinsic neurons and not to neocortical afferents

Dopamine D₂ receptors, labeled with ³H]spiroperidol or ³H]sulpiride, show a lateral-to-medial gradient in the caudate-putamen, with a more than two-fold greater density laterally than medially. It has been thought that D₂ receptors are located on at least two neuronal elements of the caudate-putamen, neurons intrinsic to this structure and axons whose cell bodies reside in the cortex. As a first step in establishing what neuronal elements underlie this heterogeneous organization of D₂ receptors, we took advantage of quantitative autoradiography to examine the association of these receptors with those elements. The present findings show that the D₂ sites are almost exclusively located on neurons whose somata reside in the caudate-putamen and are not located on terminals of corticostriatal axons. A detailed comparison of the distribution of histochemically identified acetylcholinesterase neurons with that of D₂ receptors in serially adjoining sections suggests a common organizational pattern.

The density of ³H]spiroperidol sites in rat caudate-putamen was determined after unilateral injection of the neurotoxin quinolinic acid into this structure or after ablation of neocortical regions. Quantification of the tissue damage was achieved by acetylcholinesterase histochemistry (following diisopropylfluoro-phosphate treatment), as well as by thionin and luxol fast staining of sections adjacent to those used for ³H]spiroperidol autoradiography. In identically treated animals, biochemical determination of the extent of tissue damage was made utilizing assays for high-affinity ³H]choline and ³H]glutamate uptake in the caudate-putamen. In quinolinic acid-injected rats, the density of D₂ sites was decreased by 90–95% at the site of complete loss of large acetylcholinesterase-positive neurons. Other animals, given ablations of specific neocortical fields (medial prefrontal, motor, somatosensory) or of the entire parietal-frontal cortex of one hemisphere, showed no loss of caudate-putamen D₂ sites unless the cortical ablation caused accompanying damage of the caudate-putamen. In the caudate-putamen of all animals there was a close correspondence between the D₂ sites and the striatal neurons (and processes) that show strong acetylcholinesterase reactivity.

We suggest that the caudate-putamen topography of D₂ sites is based largely on the internal organization of this structure and may preferentially involve acetylcholine-containing intrinsic neurons.