PHARMACOLOGY AND PHYSIOLOGY OF THE SUBSTANTIA NIGRA AND BASAL GANGLIA

黑质和基底神经节的药理学和生理学

• 批准号: 4696817
• 负责人: J R WALTERS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4696817
• 关键词: Huntington's disease; Parkinson's disease; central nervous system; central nervous system disorders; centrally acting drug; cerebrospinal fluid; dopamine; drug metabolism; evoked potentials; extrapyramidal disorder; fluorimetry; gamma aminobutyrate; glutamate decarboxylase; mental disorder chemotherapy; neurochemistry; neuromuscular disorder chemotherapy; neuropharmacology; neurotoxins; neurotransmitter biosynthesis; neurotransmitter metabolism; neurotransmitters; pilocarpine; probenecid; radioimmunoassay; radiotracer; substantia nigra

1) Structure and Function of Dopamine Receptors. To better understand and define the dopamine receptors mediating the effects of dopamine agonists in the basal ganglia, potency series have been determined for a series of selective and nonselective dopamine agonists at dopamine autoreceptors and postsynaptic receptors. The results support the idea that the dopamine autoreceptors, located on the substantia nigra pars compacta dopamine neurons, are of the classic D-2 subtype. However, at least some of the postsynaptic copamine receptors mediating nigra cell activity appear to be relatively insensitive not only to the selective D-1 agonist, but to the selective D-2 dopamine agonists as well. This suggests that these receptors are not classic D-2, or D-1, receptors. In addition, there appears to be an interaction between the receptors mediating the effects of the nonselective dopamine agonists and the D-1 receptors; the consequences of stimulating the former is attenuated by a D-1 receptor antagonist. 2) Substantia Nigra Pars Reticulata in Epilepsy. It has been suggested that enhancement of GABAergic transmission within the substantia nigra prevents the motor manifestations of kindled seizures. We have recorded single unit activity of substantia nigra neurons during electrical seizures in components of the EEG, indicating that the substantia nigra is directly transmitting seizure activity in the kindled rat. To explore further the importance of this area as a therapeutic target in epilepsy, we have evaluated the effects of a diverse group of anticonvulsant drugs on these cells. Consisstent inhibitory effects on tonic activity were produced only by drugs with proposed GSBAergic mechanisms. 3) Glutamate and Related Neurotransmitter in the Substantia Nigra. At least 2 and perhaps 3 excitatory amino acid receptor types have been demonstrated or both the substantia nigra dopamine and pars reticulata cells neuron. Moreover, n-methyl-D-asparate preferring receptors on the dopamine neurons mediate a previously undescribed firing pattern for these cells.

1)多巴胺受体的结构和功能。 更好地理解和 定义多巴胺受体介导的多巴胺激动剂的作用， 基底神经节，效力系列已经确定了一系列的 多巴胺自身受体的选择性和非选择性多巴胺激动剂， 突触后受体 结果支持了多巴胺 自身受体，位于黑质多巴胺前叶 神经元是典型的D-2亚型。 然而，至少有一些 介导黑质细胞活性的突触后可帕胺受体似乎是 不仅对选择性D-1激动剂相对不敏感， 选择性D-2多巴胺激动剂。 这表明这些 受体不是典型的D-2或D-1受体。 此外还有 似乎是受体之间的相互作用介导的影响， 非选择性多巴胺激动剂和D-1受体; D-1受体拮抗剂可减弱对前者的刺激。 2)癫痫患者的黑质网状部 有人建议 黑质内GABA能传递的增强 防止癫痫发作的运动表现。 我们记录了 电惊厥时黑质神经元的单位放电 在EEG的成分中，表明黑质直接 在点燃的大鼠中传递癫痫发作活动。 进一步探寻是否 该区域作为癫痫治疗靶点的重要性 评估了一组不同的抗惊厥药物对这些 细胞 对紧张性活动的持续抑制作用仅产生于 通过具有GSBA能机制的药物。 3)黑质谷氨酸及其相关神经递质。 在 至少有2种，也许有3种兴奋性氨基酸受体类型， 证明或黑质多巴胺和网状部 神经元细胞 此外，N-甲基-D-谷氨酸偏好受体上， 多巴胺神经元介导了一种以前未描述的放电模式， 细胞