Napier T C, Mitrovic I, Churchill L, Klitenick M A, Lu X Y, Kalivas P W
Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois, USA.
Neuroscience. 1995 Nov;69(1):59-70. doi: 10.1016/0306-4522(95)00218-8.
The ventral pallidum of the basal forebrain contains a high concentration of substance P and receives a massive projection from the nucleus accumbens. The present study was designed to determine whether the accumbens serves as a source for substance P-containing fibers in the ventral pallidum and characterize the function of this tachykinin peptide within the ventral pallidum. By combining in situ hybridization for messenger RNA of the substance P prohormone, beta-preprotachykinin, with Fluoro-Gold retrograde labeling from iontophoretic deposits in the ventral pallidum, a population of substance P-containing neurons was demonstrated in the shell and core components of the nucleus accumbens and the ventromedial striatum. The function of substance P within the ventral pallidum was characterized at the level of the single neuron, and the behaving animal. Electrophysiological assessment revealed that approximately 40% of the 97 ventral pallidal neurons tested were readily excited by microiontophoretic applications of substance P or a metabolically stable agonist analog, DiMeC7 [(pGlu5, MePhe8, MeGly9)-substance P5-11]. Response characteristics were distinguished from glutamate-induced excitations by a slower onset and longer duration of action. Recording sites of tachykinin-sensitive neurons were demonstrated to be located throughout the ventral pallidum and within high densities of fibers exhibiting substance P-like immunoreactivity. When behaving rats received microinjections of DiMeC7 into this same region, the animals displayed an increase in motor activity, with a response threshold of 0.1nmol per hemisphere. These results verify the existence of a substantial substance P-containing projection from the nucleus accumbens to the ventral pallidum. The projection likely serves to excite ventral pallidal neurons for these neurons readily increased firing following local exposure to tachykinins. Furthermore, an increase in motor behavior appears to be a consequence of this neuronal response.
基底前脑的腹侧苍白球含有高浓度的P物质，并接受来自伏隔核的大量投射。本研究旨在确定伏隔核是否是腹侧苍白球中含P物质纤维的来源，并描述这种速激肽在腹侧苍白球内的功能。通过将P物质前激素β-前速激肽原的信使核糖核酸原位杂交与腹侧苍白球离子电渗沉积的荧光金逆行标记相结合，在伏隔核的壳部和核心部分以及腹内侧纹状体中发现了一群含P物质的神经元。在单个神经元和行为动物水平上对腹侧苍白球内P物质的功能进行了表征。电生理评估显示，在测试的97个腹侧苍白球神经元中，约40%的神经元通过微离子电渗法应用P物质或代谢稳定的激动剂类似物DiMeC7 [（pGlu5，MePhe8，MeGly9）-P物质5-11]很容易被兴奋。反应特征与谷氨酸诱导的兴奋不同，其起效较慢且作用持续时间较长。速激肽敏感神经元的记录位点被证明位于整个腹侧苍白球以及显示P物质样免疫反应性的高密度纤维内。当行为大鼠在同一区域接受DiMeC7的微量注射时，动物的运动活动增加，每侧半球的反应阈值为0.1nmol。这些结果证实了从伏隔核到腹侧苍白球存在大量含P物质的投射。这种投射可能用于兴奋腹侧苍白球神经元，因为这些神经元在局部暴露于速激肽后很容易增加放电。此外，运动行为的增加似乎是这种神经元反应的结果。
