PHARMACOLOGY AND PHYSIOLOGY OF THE SUBSTANTIA NIGRA AND BASAL GANGLIA

1)基底节D1型和D2型多巴胺受体的体外研究 细胞内记录技术在纹状体切片中的应用研究 找到诱发的尖峰活动的模式和方向/程度 电流-电压关系数据中的整流不会在 6周(DA)细胞损伤后的纹状体神经元。然而，在 在电流-电压关系中表现出名义整流的神经元， 一个描述超极化膜早期开始的时间常数 瞬变时间明显小于对照组。SKF38393效果 DA细胞损伤后神经元兴奋性改变，但该药 作用与DL受体无关，这引发了关于体外使用的问题 SKF 38393为典型的D1激动剂。 2)多巴胺激动剂的体内效应：苍白球。两个截然不同的 苍白球细胞的类型已经根据它们的 细胞外波形和对DA受体刺激的反应。这个 细胞对全身阿朴吗啡的相反反应引发了关于 基底节环路。 3)基底节多巴胺耗竭的后果。证据： 观察到的D1介导的效应的变异性：在利血平治疗后， DL激动剂给药后，大鼠的放电频率增加。 黑质网状部神经元，这种作用与 在6-OHDA损毁的大鼠身上观察到了这一点。而且，最终的结果是 在利血平制剂中刺激两种受体亚型， 事实上，与只有DL受体时得到的结果相反 受到刺激。 4)兴奋性氨基酸受体亚型AMPA和NMDA在脑缺血再灌注损伤中的作用 基底节功能。NMDA拮抗剂地佐西平对血管紧张素转换酶无影响。 纹状体、苍白球和脑实质的自发活动 黑质网状部。尽管内侧足突神经元部分地 地佐西平(MK 801)对其有抑制作用。相比之下，AMPA拮抗剂NBQX 产生了与剂量相关的对大脑球活动的部分抑制 苍白球、黑质网状部和尾状神经元时 有系统地给予。局部注射NBQX可降低苍白球活动和 部分阻断激活丘脑底核的作用。因此， 补充性谷氨酸输入是一些自发的 基底节不同核团的活动。谷氨酸的研究 拮抗剂氯胺酮和MK801已表明MK801不出现 是一种有效的麻醉剂；氯胺酮麻醉与 NOR导致NMDA受体复合体的弥漫性阻断。

1) Dl and D2 Dopamine Receptors in Basal Ganglia: In Vitro Studies. Studies in striatal slices utilizing intracellular recording techniques find patterns of evoked spike activity and the direction/extent of rectification in current-voltage relationship data are not altered in striatal neurons following 6- week (DA) cell lesion. However, among neurons exhibiting nominal rectification in current-a-voltage relations, a time constant describing the early onset of hyperpolarizing membrane transients was significantly smaller than in control. SKF38393 effects on neuronal excitability are altered after DA cell lesion but this drug's action is unrelated to Dl receptors, raising questions about in vitro use of SKF 38393 as prototypic D1 agonist. 2) In Vivo Effects of Dopamine Agonists: Globus Pallidus. Two distinct globus pallidus cell types have been identified based on their extracellular waveforms and response to DA receptor stimulation. The cells' opposite responses to systemic apomorphine raises questions about basal ganglia circuitry. 3) Consequences of Dopamine Depletion in the Basal Ganglia . Evidence for variability in D1- mediated effects observed: after reserpine treatment, Dl agonist administration leads to an increase in the firing rate of the substantia nigra pars reticulata neurons, an effect exactly opposite to that observed in the 6-OHDA lesioned rats. Moreover, the net result of stimulating both receptor subtypes in the reserpinized preparation was, in fact, opposite to the result obtained when only Dl receptors were stimulated. 4) Role of Excitatory Amino Acid Receptor Subtypes, AMPA, and NMDA in Basal Ganglia Function. The NMDA antagonist dizocilpine had no effect on spontaneous activity in the striatum, globus pallidus, and substantia nigra pars reticulata. Although entopeduncular neurons were partially inhibited by dizocilpine(MK 801). In contrast, the AMPA antagonist NBQX produced a dose-related partial inhibition of activity in the globus pallidus, substantia nigra pars reticulata, and caudate neurons when given systemically. Local infusion of NBQX reduced pallidal activity and partially blocked effects of activating the subthalamic nuclei. Thus, tonic glutamate input serves as a driving force behind some spontaneous activity in various nuclei in the basal ganglia. Studies with glutamate antagonists ketamine and MK801 have indicated that MK801 does not appear to be an effective anesthetic; ketamine anesthesia is neither associated with nor results in a diffuse blockade of the NMDA receptor complex.