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 diisopropylfluorophosphate 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.
D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D001345:Autoradiography; D002421:Caudate Nucleus / Q000032:analysis* / Q000187:drug effects; D002540:Cerebral Cortex / Q000032:analysis*; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D008297:Male; D009434:Neural Pathways / Q000032:analysis; D011699:Putamen / Q000032:analysis* / Q000187:drug effects; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000032:analysis*; D017448:Receptors, Dopamine D2; D013134:Spiperone; D013469:Sulpiride
D011805:Quinolinic Acids; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D013134:Spiperone; D013469:Sulpiride; D000110:Acetylcholinesterase; D017378:Quinolinic Acid