Schiffmann S N, Vanderhaeghen J J
Laboratory of Neurophysiology, Neuropathology and Neuropeptides Research, Erasme Hospital, Faculty of Medicine, Université Libre de Bruxelles, Belgium.
Neuroscience. 1993 Jun;54(3):681-9. doi: 10.1016/0306-4522(93)90239-c.
Interactions between dopamine and neurotensin or dopamine and cholecystokinin have been demonstrated in the basal ganglia. Disruption of nigrostriatal dopaminergic transmission results in a dramatic increase in neurotensin messenger RNA and in an induction of cholecystokinin messenger RNA in the striatum. Interaction between striatal dopaminergic and adenosinergic systems have also been reported. Adenosine and the adenosine receptor antagonist, caffeine, regulate gene expression in the striatum. In the present study, in situ hybridization histochemistry was used to investigate the putative regulation of neurotensin and cholecystokinin messenger RNA expression by caffeine in the rat striatum. Using this method, cholecystokinin messenger RNA was undetectable and neurotensin messenger RNA very sparse in the normal striatum. Chronic caffeine administration induced a dramatic increase in neurotensin messenger RNA in the subcallosal region of the caudate-putamen and a moderate increase in the shell sector of the accumbens nucleus. Similarly, caffeine induced a significant striatal expression of cholecystokinin messenger RNA in the dorsolateral and ventrolateral quadrants but was not restricted to the subcallosal area. At the cellular level, this corresponded to a significant labeling of a moderate to high density of medium-sized striatal neurons. These distributions were identical to those of neurotensin and cholecystokinin messenger RNAs observed in the case of disruption of dopaminergic transmission. We therefore concluded that in the intact striatum normally innervated by dopaminergic fibers, caffeine, probably acting through a presynaptic A2 receptor, induced a relative dopamine depletion which in turn led to the induction of neurotensin and cholecystokinin expression in subsets of striatal neurons.
多巴胺与神经降压素之间或多巴胺与胆囊收缩素之间的相互作用已在基底神经节中得到证实。黑质纹状体多巴胺能传递的破坏导致纹状体中神经降压素信使核糖核酸显著增加以及胆囊收缩素信使核糖核酸的诱导。纹状体多巴胺能系统与腺苷能系统之间的相互作用也有报道。腺苷和腺苷受体拮抗剂咖啡因可调节纹状体中的基因表达。在本研究中，采用原位杂交组织化学方法研究咖啡因对大鼠纹状体中神经降压素和胆囊收缩素信使核糖核酸表达的假定调节作用。使用该方法，在正常纹状体中未检测到胆囊收缩素信使核糖核酸，神经降压素信使核糖核酸也非常稀少。长期给予咖啡因可导致尾壳核胼胝体下区域的神经降压素信使核糖核酸显著增加，伏隔核壳区适度增加。同样，咖啡因可诱导背外侧和腹外侧象限的纹状体中胆囊收缩素信使核糖核酸显著表达，但不限于胼胝体下区域。在细胞水平上，这对应于中等密度到高密度的中等大小纹状体神经元的显著标记。这些分布与多巴胺能传递破坏时观察到的神经降压素和胆囊收缩素信使核糖核酸的分布相同。因此，我们得出结论，在正常由多巴胺能纤维支配的完整纹状体中，咖啡因可能通过突触前A2受体起作用，诱导相对的多巴胺耗竭，进而导致纹状体神经元亚群中神经降压素和胆囊收缩素表达的诱导。
