Chang R S, Tran V T, Snyder S H
Brain Res. 1980 May 19;190(1):95-110. doi: 10.1016/0006-8993(80)91162-2.
Selective neuronal lesions have been utilized in efforts to localize binding sites in rat brain for beta-adrenergic, gamma-aminobutyric acid (GABA), histamine H1 and benzodiazepine receptors. The various receptors respond differentially to lesions both in extent of change and in time course. After kainate lesions in the corpus striatum, benzodiazepine receptors are depleted up to 45% at 45--78 days but are unaffected after 7 days. By contrast striatal GABA receptors are increased at 7 days but depleted at later times. Thus both striatal benzodiazepine and GABA receptors appear to be associated at least in part with intrinsic neurons. In the cerebellum both benzodiazepine and GABA receptors are reduced in kainate treated rats and in Nervous mice, mutants which lack Purkinje cells. The most pronounced dissimilarity between benzodiazepine and GABA receptors occurs in Weaver mice, which selectively lack granule cells and display a 60% reduction in GABA receptors but a 40% augmentation in benzodiazepine receptors. A major portion of cerebellar GABA receptors, therefore, appear to be localized to granule cells. Striatal beta-adrenergic receptors are reduced following intrastriatal kainate injections but are unaffected by cerebral cortex ablation, suggesting an association with intrinsic neurons but not with axon terminals of the corticostriate pathway. While intraventricular injections of 6-hydroxydopamine enhance [3H]dihydroalprenolol binding to beta-adrenergic receptors in the cerebral cortex and hippocampus, such binding is not augmented in the corpus striatum, brain stem, midbrain or thalamus-hypothalamus by this treatment. Moreover, medial forebrain bundle lesions, which destroy ascending adrenergic neurons, fail to alter cerebral cortical or striatal beta-adrenergic receptors. Thus denervation-elicited increases in beta-adrenergic receptors vary with brain region and the type of denervating lesion. Histamine H1-receptors are the most resistant of all to neuronal lesions. In the corpus striatum [3H]mepyramine binding is unaffected by cerebral cortex ablation, nigral injections of 6-hydroxydopamine or brain stem hemisection. In the hippocampus, medial forebrain bundle lesions, intrahippocampal kainate injection, and fimbria and fornix transection largely fail to alter [3H]mepyramine binding. Accordingly, a major portion of these receptors may be associated with nonneuronal elements such as glia or blood vessels.
为了在大鼠脑中定位β-肾上腺素能、γ-氨基丁酸（GABA）、组胺H1和苯二氮䓬受体的结合位点，人们利用了选择性神经元损伤。各种受体对损伤的反应在变化程度和时间进程上都有所不同。在纹状体注射海人酸损伤后，苯二氮䓬受体在45 - 78天内减少多达45%，但在7天后不受影响。相比之下，纹状体GABA受体在7天时增加，但在后期减少。因此，纹状体苯二氮䓬受体和GABA受体似乎至少部分与内在神经元相关。在小脑，在接受海人酸处理的大鼠和缺乏浦肯野细胞（Purkinje cells）的突变体Nervous小鼠中，苯二氮䓬受体和GABA受体都减少。苯二氮䓬受体和GABA受体之间最显著的差异出现在Weaver小鼠中，它们选择性地缺乏颗粒细胞，GABA受体减少60%，而苯二氮䓬受体增加40%。因此，小脑的大部分GABA受体似乎定位于颗粒细胞。纹状体内注射海人酸后，纹状体β-肾上腺素能受体减少，但大脑皮质切除对其无影响，这表明它与内在神经元相关，而与皮质纹状体通路的轴突终末无关。虽然脑室内注射6-羟基多巴胺可增强[3H]二氢阿普洛尔与大脑皮质和海马中β-肾上腺素能受体的结合，但这种处理在纹状体、脑干、中脑或丘脑-下丘脑并未增强这种结合。此外，破坏上行肾上腺素能神经元的内侧前脑束损伤，未能改变大脑皮质或纹状体的β-肾上腺素能受体。因此，去神经支配引起的β-肾上腺素能受体增加因脑区和去神经支配损伤的类型而异。组胺H1受体是所有受体中对神经元损伤最具抗性的。在纹状体，[3H]美吡拉敏结合不受大脑皮质切除、黑质注射6-羟基多巴胺或脑干半切的影响。在海马，内侧前脑束损伤、海马内注射海人酸以及穹窿和穹窿柱横断在很大程度上未能改变[3H]美吡拉敏结合。因此，这些受体的大部分可能与非神经元成分如神经胶质或血管相关。
