Human striatal dopamine receptors are organized in compartments.

Abstract

Dopamine (D2) receptors visualized in postmortem human striatum by quantitative autoradiography of [3H]spiroperidol binding are organized into circumscribed zones of low receptor density separated from other such zones by regions of higher D2 density. The D2-rich zones of the caudate nucleus and putamen contain twice the binding of D2-poor zones. The Hill coefficient, obtained from saturation analysis of [3H]spiroperidol binding to thin sections of human striatum, gave a value near unity, indicating the binding was occurring to a single type of site. The patchiness of [3H]spiroperidol binding was unaltered by postincubation removal of lipid from the tissue sections, indicating that a differential absorption of tritium in white and grey matter does not account for the heterogeneous distribution. The D2-rich and D2-poor regions appear to form labyrinths oriented in the anterior-posterior axis and are typically aligned with, respectively, acetylcholinesterase-rich and -poor compartments as visualized on stained adjacent sections. Thus, the distribution of dopamine D2 receptors conforms to the "striosomal" organization of the human caudate-putamen, a finding that suggests that this receptor subtype may mediate the influence of dopamine on distinct neurochemical compartments within the structure. The brain transmitter dopamine has profound effects on mammalian movement and sensorimotor coordination. The massive ascending projections of the ventral midbrain dopaminergic neurons have been well characterized, and strong evidence points to a critical role of this system in several major neurological disorders. Abnormalities of dopaminergic transmission in human brain contribute to Parkinson disease, drug-induced dyskinetic reactions, and the cognitive disturbances of acute psychotic states (1-3). The D2 receptor (4) appears to be the principal site of action of dopamine receptor agonists and antagonists on behavior of humans and animals (5, 6). An understanding of how the D2 receptor contributes to the diversity of dopaminergic influences in the human necessitates that the distribution of these sites be determined with a high degree of anatomical resolution. This has been achieved though the application of the autoradiographic approach for the visualization of dopamine D2 receptors (7) and of computer-assisted quantitative autoradiography (8).In the rodent striatum, a sharp lateral-to-medial gradient of D2 receptors has been observed (8, 9) that appears to correspond to a similar gradient of markers for acetylcholine (AcCho) nerve terminal density (10). (8)(9)(10)(15)(16)(17). Briefly, coronal sections 20 ,um thick were cut at -15°C in a cryostat and thaw-mounted onto gelatin-coated glass slides. Immediately prior to incubation with radioligands, the sections were thawed and dried at room temperature, then transferred to glass dishes containing the preincubation buffer (50 mM Tris HCl, pH 7.1/120 mM NaCl/5 mM KCl/2 mM CaCl2/1 mM MgCl2/1 mM ascorbic acid) for 5 min at 22°C. Then Computer-Assisted Image Analysis...

Distribution of Dopamine D3 Receptor Expressing Neurons in the Human Forebrain Comparison with D2 Receptor Expressing Neurons

“…In agreement with data reported earlier (Joyce et al 1986;Murray et al 1994), the concentration of D 2 receptors was found to be highest in the rostral CN and Pu, with the sites distributed evenly through the dorsoventral extent of the striatum (Table 2 and Figure 1A). In contrast, D 3 receptors were more abundant in the NAC and ventral aspect of the rostral Pu and were concentrated in areas of dense binding giving both structures a patchy appearance (Table 2 and Figure 1B) as reported previously (Murray et al 1994;Gurevich et al 1997).…”

Loss of Dopamine D2 Receptors in Alzheimer's Disease with Parkinsonism But Not Parkinson's or Alzheimer's Disease

“…The D2 receptor family includes three subtypes, names D 2 , D 3 , and D 4 , (Sibley et al 1993), which exhibit distinct pharmacological properties and are concentrated in human brain in different regions (Joyce and Meador-Woodruff 1997 (Murray et al 1994); whereas [ 3 H]spiroperidol has low affinity for the D 3 receptor (Sokoloff et al 1990). It is now clear that D 2 -like receptors labeled with [ 3 H]spiroperidol (Joyce et al 1986a) have a distribution different from that of D 2 and D 3 receptors labeled with [ 125 I]epidepride in striatum. Murray et al 1994).…”

“…This system enabled the autoradiographic images to be digitized, and the mean optical density of each brain region of interest was converted to a value of fmol/mg protein. For autoradiographs obtained by sections labeled with a 3 H-ligand, a standard curve for 3 H based on calibrations of low activity 3 H-plastic standards to 3 H-isoleucine-tissue mash standards was used (Joyce et al 1986a). For autoradiographs obtained by sections labeled with a 125 -ligand, standards calibrated against 125 I-tissue mash standards for the appropriate exposure time was used according to the method described by Artymyshyn et al (1990).…”

The correlative triad among aging, dopamine, and cognition: Current status and future prospects

“…Although a proportion of the D 1 and D 2 receptors are co-localized on the same neurons, D 1 receptors are mainly expressed in neurons in the ''direct'' striatonigral feedback pathway, whereas D 2 receptors are expressed in ''indirect'' pathways that include interneurons (Gerfen et al, 1995;Hersch et al, 1995). At a histological level, this differential organization corresponds to the observation that D 1 neurons are primarily located in striosomes, whereas D 2 neurons are preferentially found in the matrix component of the striatum (Joyce et al, 1986;Graybiel et al, 1994).…”