Rao P A, Molinoff P B, Joyce J N
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia 19104-6141.
Brain Res Dev Brain Res. 1991 Jun 21;60(2):161-77. doi: 10.1016/0165-3806(91)90045-k.
The ontogeny of D1 and D2 dopamine (DA) receptors in rat basal ganglia was examined by quantitative autoradiography using the iodinated ligands [125I]SCH 23982 and [125I]iodobenzamide [( 125I]IBZM), respectively. Temporal and spatial differences in the development of the receptor subtypes were observed. Scatchard transformation of saturation isotherms conducted at postnatal day 10 (P10) and P60, showed that there was no age-related change in the affinity of [125I]SCH 23982 binding to D1 receptors (Kd = 2.6 nM) but there was a significant increase in the Bmax (771 compared to 2032 fmol/mg protein, P = 0.002). A statistically significant difference in Kd was noted between ages P10 and P60 for [125I]IBZM labelling of D2 receptors (0.62 vs 1.00 nM, respectively, P less than 0.01). A significant increase in the Bmax (211 and 721 fmol/mg protein, P less than 0.01) was also observed. D1 receptors were visible as distinct patches at P1. The highest density was found in the ventrolateral caudate-putamen (CPu). By P5 the patches were found in all subregions of the CPu and nucleus accumbens. Between P7 and P10 the binding became distinctly less patchy due to a marked increase in the density of D1 receptors in non-patch (matrix) regions. Adult levels of receptor were seen by P30. The concentration of DA (measured by HPLC) and binding of [3H]mazindol to DA uptake sites in whole striatum showed similar and nonlinear increases with age. The age-related change in the topography of binding sites for [3H]mazindol was similar to that of D1 receptors at the same ages. Both D2 receptors and [3H]hemicholinium-3 (HC-3) binding to high affinity transport sites for choline developed initially in the dorso-lateral CPu. Their topography was largely overlapping but distinct from that of the D1 receptor. D2 receptors were not consistently observed until P3 in the CPu, and zones of enriched binding were aligned with zones of low density for D1 receptors. The density of D2 receptors reached adult levels by P30. The differential development of the DA receptors was also evident in the substantia nigra (SN) and globus pallidus (GP). D1 receptors were found in SN prior to the appearance of D2 receptors and throughout development the density was greater in pars reticulata than in pars compacta, whereas the density of D2 receptors was higher in the pars compacta. At all ages the density of D1 receptors was greater than the density of D2 receptors in the GP and reached adult levels before reaching it in the CPu or SN.(ABSTRACT TRUNCATED AT 400 WORDS)
分别使用碘化配体[125I]SCH 23982和[125I]碘苯甲酰胺[（125I）IBZM]，通过定量放射自显影法研究了大鼠基底神经节中D1和D2多巴胺（DA）受体的个体发生。观察到受体亚型发育的时间和空间差异。在出生后第10天（P10）和P60进行的饱和等温线的Scatchard转换表明，[125I]SCH 23982与D1受体结合的亲和力没有与年龄相关的变化（Kd = 2.6 nM），但Bmax有显著增加（分别为771和2032 fmol/mg蛋白质，P = 0.002）。对于[125I]IBZM标记的D2受体，在P10和P60年龄之间观察到Kd有统计学显著差异（分别为0.62和1.00 nM，P小于0.01）。还观察到Bmax有显著增加（分别为211和721 fmol/mg蛋白质，P小于0.01）。D1受体在P1时可见为明显的斑块。在腹外侧尾状核-壳核（CPu）中发现密度最高。到P5时，在CPu和伏隔核的所有亚区域都发现了斑块。在P7到P10之间，由于非斑块（基质）区域中D1受体密度的显著增加，结合明显变得不那么呈斑块状。到P30时可见到成年水平的受体。全纹状体中DA的浓度（通过高效液相色谱法测量）和[3H]吗茚酮与DA摄取位点的结合显示出与年龄相似的非线性增加。[3H]吗茚酮结合位点的地形与相同年龄的D1受体的地形变化相似。D2受体和[3H]半胆碱-3（HC-3）与胆碱的高亲和力转运位点的结合最初都出现在背外侧CPu中。它们的地形在很大程度上重叠，但与D1受体的地形不同。直到P3在CPu中才始终观察到D2受体，并且结合丰富的区域与D1受体低密度区域对齐。D2受体的密度到P30时达到成年水平。DA受体的差异发育在黑质（SN）和苍白球（GP）中也很明显。在D2受体出现之前在SN中就发现了D1受体，并且在整个发育过程中，网状部的密度大于致密部，而致密部中D2受体的密度更高。在所有年龄，GP中D1受体的密度都大于D2受体的密度，并且在CPu或SN达到成年水平之前就达到了成年水平。（摘要截短至400字）
