CCK AND MIDBRAIN DA SYSTEMS--SPECIFICITY OF ACTIONS

八肽胆囊收缩素（CCK-8）存在于中脑多巴胺 （DA）-含有神经元，似乎作为一个共同的递质。 的 这些DA神经元在目前病因学假设中的重要性， 治疗几种神经和精神疾病需要， 它们的生理学和药理学反应性良好， 明白 近年来，人们对这种受体有了更多的了解， 这些亚型介导CCK-8对DA神经元的作用，但仍有许多 了解CCK-8在中脑的作用范围和部位。 本申请中提出的研究旨在评估可能的 CCK-8调节电生理效应的作用部位 在麻醉大鼠中DA神经元的活性。 中缝背核向中脑的多巴胺能传入 影响DA神经元的电生理活动。 上 一组拟议的实验，CCK-8与以下效应的相互作用 中缝背核刺激（和血清素本身对 将评价黑质纹状体和中脑DA神经元活性。 黑质网状部（SNr）的非DA中间神经元。 影响黑质DA能神经元的活动， 本地释放的CCK-8。 SNr也是非DA黑质丘脑 和黑质顶盖神经元，它们是锥体外系的重要环节， 运动系统。 因此，CCK-8对SNr活性的影响 黑质丘脑和黑质顶盖的中间神经元和逆向识别 神经元将被确定。 神经毒素6-OHDA会导致 DA神经元的神经元，并用于产生帕金森氏症的动物模型， 疾病 剩下的DA神经元的药理学反应 已经发生了很大的变化 因为他们之间的亲密关系 CCK-8和DA之间，可能是剩余的反应性 6-OHDA损伤大鼠DA神经元对CCK-8的反应发生变化。 这样的改变 在响应性将有重要的影响，监管 损伤大鼠DA神经元功能，并推断某些疾病 states. 在最后一组实验中，CCK-8对剩余的 将测试6-OHDA损伤大鼠中的DA神经元。 的影响 中脑DA细胞体区DA水平和CCK-8水平的损害 和DA细胞投射位点。

Cholecystokinin octapeptide (CCK-8) is present within midbrain dopamine (DA)-containing neurons and appears to act as a cotransmitter. The importance of these DA neurons in current hypotheses of the etiology and treatment of several neurological and psychiatric disorders requires that their physiology and their pharmacological responsiveness be well understood. In recent years, much has been learned about the receptor subtypes which mediate the effects of CCK-8 on DA neurons, but much remains to be learned about the scope and sites of CCK-8 actions In the midbrain. The studies proposed in this application are intended to evaluate possible sites of action for modulatory effects of CCK-8 on the electrophysiological activity of DA neurons in anesthetized rats. The serotonergic input to the midbrain from the dorsal raphe nucleus Influences the electrophysiological activity of DA neurons. In the first set of proposed experiments, Interactions of CCK-8 with the effects of dorsal raphe nucleus stimulation (and with serotonin itself on nigrostriatal and mesoaccumbal DA neuronal activity will be evaluated. Non-DA interneurons in the substantia nigra pars reticulata (SNr). Influence the activity of nigral DA neurons and may be accessible to locally released CCK-8. The SNr is also the source of non-DA nigrothalamic and nigrotectal neurons which are important links in the extrapyramidal motor system. Thus, the effects of CCK-8 on the activity of SNr interneurons and antidromically identified nigrothalamic and nigrotectal neurons will be determined. The neurotoxin 6-OHDA causes the degeneration of DA neurons and is used to produce an animal model of Parkinson's disease. The pharmacological responsiveness of the remaining DA neurons has been shown to be greatly altered. Because of the intimate relationship between CCK-8 and DA, it is possible that the responsiveness of remaining DA neurons to CCK-8 is changed in the 6-OHDA-lesioned rat. Such a change In responsiveness would have important implications for the regulation of DA neuronal function in the lesioned rat and, by inference, certain disease states. In the last set of experiments, the effects of CCK-8 on remaining DA neurons in the 6-OHDA-lesioned rat will be tested. The effects of the lesions on DA levels and CCK-8 levels in the midbrain DA cell body region and in DA cell projection sites will also be determined.