Seroogy K B, Dangaran K, Lim S, Haycock J W, Fallon J H
Department of Anatomy and Neurobiology, University of California, Irvine 92717.
J Comp Neurol. 1989 Jan 15;279(3):397-414. doi: 10.1002/cne.902790306.
The coexistence of cholecystokinin- and tyrosine hydroxylase-like immunoreactivities within neurons of the rat ventral mesencephalon was analyzed by using an indirect immunofluorescence technique for the simultaneous demonstration of two antigens in the same tissue section. A high degree of colocalization was observed in the substantia nigra pars compacta, in which 80-90% of all labeled neurons at rostral and up to 70% at intermediate levels contained both cholecystokinin and tyrosine hydroxylase. At caudal levels, the incidence of colocalization declined to approximately 30-50%. All of the immunoreactive perikarya in the substantia nigra pars lateralis were labeled with both substances. Other areas of the ventral midbrain that exhibited a moderate proportion of neurons immunoreactive for both cholecystokinin and tyrosine hydroxylase included the ventral tegmental area, interfascicular nucleus, and rostral and caudal linear nuclei. In addition, coexistence was occasionally observed within neurons of the central and ventral periaqueductal gray matter, supramammillary region, peripeduncular region, retrorubral field, and extremely rarely, within the substantia nigra pars reticulata. Cell bodies containing tyrosine hydroxylase-like immunoreactivity (indicative of dopamine) usually outnumbered those containing the peptide except in the supramammillary region and in the ventral periaqueductal gray matter, where the cholecystokinin perikarya were present in higher numbers. The double-labeling colocalization technique was combined with fluorescence retrograde tracing to determine some of the forebrain projections of these neurons. Ventral midbrain neurons containing both cholecystokinin and tyrosine hydroxylase were found to project to the caudate-putamen, nucleus-accumbens, prefrontal cortex, and amygdala. These projections originated from neurons located predominantly in the substantia nigra pars compacta and the ventral tegmental area. Thus, cholecystokinin occurs within the well-known dopaminergic nigrostriatal pathway in the rat. Overall, these results demonstrate that a significant proportion of the dopamine neurons giving rise to the ascending mesotelencephalic projections also contain the peptide cholecystokinin.
采用间接免疫荧光技术在同一组织切片中同时显示两种抗原，分析了大鼠腹侧中脑神经元中胆囊收缩素样免疫反应性和酪氨酸羟化酶样免疫反应性的共存情况。在黑质致密部观察到高度的共定位，其中在嘴侧所有标记神经元的80 - 90%以及在中间水平高达70%的神经元同时含有胆囊收缩素和酪氨酸羟化酶。在尾侧水平，共定位发生率降至约30 - 50%。黑质外侧部所有免疫反应性核周体均被两种物质标记。腹侧中脑的其他区域，显示出中等比例的对胆囊收缩素和酪氨酸羟化酶均有免疫反应性的神经元，包括腹侧被盖区、束间核以及嘴侧和尾侧线性核。此外，在中脑导水管周围灰质中央部和腹侧部、乳头体上区、脚周区、红核后区的神经元中偶尔也观察到共存情况，在黑质网状部则极为罕见。除了乳头体上区和中脑导水管周围灰质腹侧部胆囊收缩素核周体数量较多外，含有酪氨酸羟化酶样免疫反应性（指示多巴胺）的细胞体通常比含有该肽的细胞体数量多。双标记共定位技术与荧光逆行追踪相结合，以确定这些神经元的一些前脑投射。发现同时含有胆囊收缩素和酪氨酸羟化酶的腹侧中脑神经元投射到尾壳核、伏隔核、前额叶皮质和杏仁核。这些投射起源于主要位于黑质致密部和腹侧被盖区的神经元。因此，胆囊收缩素存在于大鼠著名的多巴胺能黑质纹状体通路中。总体而言，这些结果表明，产生中脑间脑上升投射的多巴胺神经元中有相当一部分也含有胆囊收缩素肽。
