Ladurelle N, Keller G, Roques B P, Daugé V
Département de Pharmacochimie Moléculaire et Structurale, U 266 INSERM, URA D 1500 CNRS, Université René Descartes (Paris V), Faculté des Sciences Pharmaceutiques et Biologiques, France.
Brain Res. 1993 Nov 19;628(1-2):254-62. doi: 10.1016/0006-8993(93)90962-m.
The effects of the local administration of cholecystokinin octapeptide (CCK8) in the posterior nucleus accumbens (N. Acc.) and of BC264 (a selective CCKB agonist) in the anterior N. Acc. on dopamine (DA) neurotransmission were studied in awake rats. Microdialysis was used to quantify the extracellular contents of DA and its two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). In the posterior N. Acc., a perfusion of 10(-5) M CCK8 for 40 min (i.e. 25 pmol) increased the extracellular levels of DA, DOPAC and HVA. In contrast, 10(-4) M BC264 perfused for 40 min (i.e. 350 pmol) into the anterior N. Acc. reduced extracellular DA but did not modify DOPAC and HVA levels. These findings suggest that the CCK-DA interactions are different in various regions of the N. Acc. and emphasize the functional heterogeneity of the N. Acc., issuing in part from its particular DA innervation (mixed CCK-DA terminals only in the posterior region) but also from the distribution of the CCK fibers and binding sites in this nucleus. This microdialysis study, using perfusions of CCK compounds in the N. Acc. of freely moving rats, shows that the CCK system might play an important regulatory role in limbic DA function.
在清醒大鼠中研究了伏隔核后部局部注射八肽胆囊收缩素(CCK8)以及伏隔核前部注射BC264(一种选择性CCKB激动剂)对多巴胺(DA)神经传递的影响。采用微透析法对DA及其两种代谢产物3,4 - 二羟基苯乙酸(DOPAC)和高香草酸(HVA)的细胞外含量进行定量分析。在伏隔核后部,灌注10(-5) M CCK8 40分钟(即25皮摩尔)可提高DA、DOPAC和HVA的细胞外水平。相反,向伏隔核前部灌注10(-4) M BC264 40分钟(即350皮摩尔)可降低细胞外DA水平,但不改变DOPAC和HVA水平。这些发现表明,CCK与DA的相互作用在伏隔核的不同区域有所不同,并强调了伏隔核的功能异质性,这部分源于其特定的DA神经支配(仅在后侧区域存在混合的CCK - DA终末),也源于该核内CCK纤维和结合位点的分布。这项在自由活动大鼠的伏隔核中灌注CCK化合物的微透析研究表明,CCK系统可能在边缘系统DA功能中发挥重要的调节作用。