Kilts C D, Coco M L, Ely T D, Bissette G, Nemeroff C B
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Ann N Y Acad Sci. 1992;668:266-76. doi: 10.1111/j.1749-6632.1992.tb27355.x.
The findings of this study extend the observations of Deutch et al. who suggested that NT in the ventral mesencephalon may be involved in the environmentally elicited activation of selectively responsive populations of mesotelencephalic dopamine neurons. The unconditioned response of NT-LI to electric footshock was observed only at an intensity of 500 microA and only in the lateral subdivision of the VTA. The selective effect of footshock stress on the NT content of a specific cell body group of the ventral mesencephalon suggests that NT mechanisms in the lateral VTA may, in part, underlie the stress-induced activation of dopamine neurons that originate in the lateral VTA. However, it should be noted that populations of dopamine neurons are activated by footshock intensities less than 500 microA, while NT concentrations of mesencephalic dopamine cell body groups are not altered by these shock intensities. The disparity weakens the possibility of a role for NT in the stress-induced activation of brain dopamine neurons unless NT mechanisms may be involved in transducing the effects of higher intensity stressors versus low intensity stressors. However, it should be noted that changes in the concentration of NT-LI represent an endpoint of unknown sensitivity and functional significance and best serve as an initial approximation of the effects of a manipulation on NT-containing neurons. It is plausible that NT mechanisms in the ventral mesencephalon may act in concert with other neuropeptides such as substance P and Met-enkephalin to transduce the effects of stressors on alterations in the activity of mesotelencephalic dopamine neurons that originate in the ventral mesencephalon. An examination of the effects of footshock stress on the content of prepro-NT mRNA in the dopamine cell body groups of the ventral mesencephalon would be of interest in assessing whether stress enhances NT gene expression or alters the characteristics of release of this neuropeptide in the ventral mesencephalon. Lacking NT receptor antagonists, it would also be of interest to determine the effects of the passive immunoneutralization of NT in the ventral mesencephalon on footshock-induced increases in the biochemically estimated activity of mesotelencephalic dopamine neurons to better understand the involvement of NT as a transducer of the effects of stress on dopamine neuronal activity. The distinct topography of conditioned versus unconditioned stress on the concentration of NT-LI in the dopamine cell body groups of the ventral mesencephalon suggests that NT may be involved in the differential activation of distinct dopamine neuronal populations by these different stressors.(ABSTRACT TRUNCATED AT 400 WORDS)
本研究结果扩展了多伊奇等人的观察结果，他们认为中脑腹侧的神经降压素（NT）可能参与环境引发的中脑边缘多巴胺神经元选择性反应群体的激活。仅在500微安的强度下，且仅在腹侧被盖区（VTA）的外侧亚区观察到NT免疫反应性对电击足底的非条件反应。电击应激对中脑腹侧特定细胞体群中NT含量的选择性作用表明，外侧VTA中的NT机制可能部分是起源于外侧VTA的多巴胺神经元应激诱导激活的基础。然而，应该注意的是，小于500微安的电击强度就能激活多巴胺神经元群体，而这些电击强度并不会改变中脑多巴胺细胞体群中的NT浓度。这种差异削弱了NT在应激诱导的脑多巴胺神经元激活中发挥作用的可能性，除非NT机制可能参与传递高强度应激源与低强度应激源的效应。然而，应该注意的是，NT免疫反应性浓度的变化代表了一个敏感性和功能意义未知的终点，充其量只是对一种操作对含NT神经元影响的初步近似。中脑腹侧的NT机制可能与其他神经肽如P物质和甲硫氨酸脑啡肽协同作用，以传递应激源对起源于中脑腹侧的中脑边缘多巴胺神经元活动改变的影响，这是有道理的。研究电击应激对中脑腹侧多巴胺细胞体群中前神经降压素原mRNA含量的影响，对于评估应激是否增强NT基因表达或改变该神经肽在中脑腹侧的释放特征将是有意义的。由于缺乏NT受体拮抗剂，确定中脑腹侧NT的被动免疫中和对电击诱导的中脑边缘多巴胺神经元生化估计活性增加的影响，以更好地理解NT作为应激对多巴胺神经元活动影响的转导因子的参与情况，也将是有意义的。中脑腹侧多巴胺细胞体群中条件性与非条件性应激对NT免疫反应性浓度的不同拓扑结构表明，NT可能参与这些不同应激源对不同多巴胺神经元群体的差异激活。（摘要截选至400字）
