Jayaraman A, Nishimori T, Dobner P, Uhl G R
Gene Neuroscience Unit, ARC/NIDA, Baltimore, Maryland.
J Comp Neurol. 1990 Jun 8;296(2):291-302. doi: 10.1002/cne.902960209.
Immunohistochemical studies of ventral tegmental area (VTA) neurons indicate that individual cells can contain dopamine as well as the neuropeptide neurotransmitters cholecystokinin (CCK) and neurotensin (NT). We have defined the distribution of the cells expressing the mRNAs encoding these two dopamine cotransmitter peptides in each of the subnuclei of the ventral tegmental area, and quantitated the extent of expression of each gene by using in situ hybridization methods. These studies reveal significant differences in the patterns of expression of each of these two genes within various subdivisions of the VTA. The rostral linear nucleus contained numerous CCK positive cells, some of which appeared to express preproCCK-mRNA at a very high level, but this nucleus contained relatively few NT-expressing cells. The parabrachialis pigmentosus contained numerous NT and CCK positive cells. The paranigralis and interfascicularis nuclei displayed positive CCK cells but with expression at only modest levels. NT cells were very few in these nuclei. The caudal linear nuclei contained the highest number of NT-expressing neurons and these cells expressed very high levels of NT mRNA. The selective distribution of these peptide genes within the VTA subnuclei may have specific consequences. Studies of the connectivity of neurons in the VTA show that the different subnuclei of this region project to several functionally and architectonically different regions of the cerebral cortex and subcortically to nuclei related to the limbic system. Results from our study show very prominent expression of CCK mRNAs in those subnuclei that project heavily to the prefrontal, other cortical areas, and the amygdaloid complex. The NT gene is expressed prominently in those subnuclei of VTA that project heavily to the entorhinal cortex and amygdaloid complex. These results provide support for a differential role for the NT-expressing neurons than that of CCK-expressing neurons of VTA in "reward" mechanisms and in drug-seeking and motivational behavior. These observations could be applied to create working hypotheses and experimental paradigms to test the differential functional activity of the subdivisions of VTA and their potential roles in the pathogenesis and treatment of drug-seeking behavior and other neuropsychiatric disorders.
腹侧被盖区（VTA）神经元的免疫组织化学研究表明，单个细胞可同时含有多巴胺以及神经肽神经递质胆囊收缩素（CCK）和神经降压素（NT）。我们已经明确了在腹侧被盖区各亚核中表达编码这两种多巴胺共递质肽的mRNA的细胞分布，并通过原位杂交方法对每个基因的表达程度进行了定量。这些研究揭示了这两个基因在腹侧被盖区不同亚区的表达模式存在显著差异。嘴侧线性核含有大量CCK阳性细胞，其中一些细胞似乎高水平表达前CCK原mRNA，但该核中表达NT的细胞相对较少。色素带旁核含有大量NT和CCK阳性细胞。黑质旁核和束间核显示有CCK阳性细胞，但表达水平仅为中等。这些核中的NT细胞非常少。尾侧线性核含有数量最多的表达NT的神经元，这些细胞高水平表达NT mRNA。这些肽基因在腹侧被盖区亚核内的选择性分布可能会产生特定的后果。对腹侧被盖区神经元连接性的研究表明，该区域的不同亚核投射到大脑皮层的几个功能和结构不同的区域，并在皮层下投射到与边缘系统相关的核团。我们的研究结果显示，CCK mRNA在那些大量投射到前额叶、其他皮层区域和杏仁复合体的亚核中表达非常突出。NT基因在腹侧被盖区那些大量投射到内嗅皮层和杏仁复合体的亚核中显著表达。这些结果支持了在“奖赏”机制以及觅药和动机行为中，腹侧被盖区表达NT的神经元与表达CCK的神经元具有不同作用的观点。这些观察结果可用于创建工作假设和实验范式，以测试腹侧被盖区分支的不同功能活动及其在觅药行为和其他神经精神疾病的发病机制及治疗中的潜在作用。
