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Dopamine receptor binding in inbred mice: strain differences in mesolimbic and nigrostriatal dopamine binding sites.

机译:近亲小鼠中的多巴胺受体结合:中胚层和黑质纹状体多巴胺结合位点的菌株差异。

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摘要

Dopamine receptors were examined by Scatchard analysis in the striatal and olfactory tubercle regions of 11 inbred mouse strains. Simultaneous determinations of the binding characteristics of 3H-labeled 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN), a dopaminergic agonist, and [3H]spiroperidol, a dopaminergic antagonist, were examined. Among the 11 strains, the equilibrium dissociation constant (Kd) for agonist binding did not vary in either the striatum or the olfactory tubercle. Similarly, no strain differences were observed in the Kd for spiroperidol in either region, although the Kd for spiroperidol in the olfactory tubercle was uniformly higher than that in the striatum. Measurement of receptor concentrations revealed strain differences of up to 2-fold for both [3H]ADTN and [3H]spiroperidol binding sites. Within each brain region, the densities of agonist and antagonist binding sites correlated significantly. However, between brain regions there was no correlation in the density of agonist or antagonist binding sites, which suggests that mesolimbic and nigrostriatal dopamine neurons may be under independent genetic control. Analysis of [3H]spiroperidol displacement by clofluperol, aceperone, cinanserin, and mianserin in four inbred mouse strains revealed that 88-90% of the striatal spiroperidol sites are dopaminergic, with the remainder being serotonergic. In contrast, 53-66% of the olfactory tubercle [3H]spiroperidol binding sites are dopaminergic and 34-47% are serotonergic. These data suggest that genetic differences in serotonin receptors and dopamine receptors may exist among inbred mouse strains.
机译:通过Scatchard分析在11个近交小鼠品系的纹状体和嗅结节区域检查了多巴胺受体。同时测定了3H标记的2-氨基-6,7-二羟基-1,2,3,4-四氢萘(ADTN)(多巴胺能激动剂)和[3H]螺哌啶醇(多巴胺能拮抗剂)的结合特性。在这11个菌株中,纹状体或嗅结节中激动剂结合的平衡解离常数(Kd)没有变化。同样,尽管在嗅结节中螺哌啶醇的Kd始终高于纹状体中的螺哌啶醇的Kd,但在两个区域中均未观察到螺哌啶醇的应变差异。受体浓度的测量结果显示,[3H] ADTN和[3H]螺哌啶醇结合位点的菌株差异最大2倍。在每个大脑区域内,激动剂和拮抗剂结合位点的密度显着相关。但是,在大脑区域之间,激动剂或拮抗剂结合位点的密度没有相关性,这表明中脑边缘和黑质纹状体多巴胺神经元可能处于独立的遗传控制之下。氯氟哌洛尔,丙酮,丙酮,米南色林在四种近交小鼠品系中对[3H]螺哌啶醇的置换分析表明,88-90%的纹状螺哌啶醇位点是多巴胺能的,其余的是血清素能的。相反,嗅结节[3H]螺哌啶醇的结合位点中有53-66%是多巴胺能的,而34-47%是血清素能的。这些数据表明,近交小鼠品系中5-羟色胺受体和多巴胺受体的遗传差异。

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