Hamilton M E, Freeman A S
Department of Pharmacology, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
Brain Res. 1995 Aug 7;688(1-2):134-42. doi: 10.1016/0006-8993(95)00518-u.
The carboxyterminal octapeptide of cholecystokinin (CCK-8) coexists with dopamine (DA) in mesolimbic neurons of the ventral tegmental area (VTA). In the present study, in vivo microdialysis in freely moving rats was used to assess the relative effects of sulfated CCK-8 (CCK-8S), unsulfated CCK-8 (CCK-8US) and CCK tetrapeptide (CCK-4), focally injected into the VTA, on DA overflow in two mesolimbic DA/CCK-8S terminal regions, the nucleus accumbens and the amygdala. Consistent with electrophysiological findings, microinjection of CCK-8S, but not CCK-8US or CCK-4, elicited increases in DA overflow in both terminal regions. In the absence of anatomical evidence of CCK-containing fibers in the VTA region, it seems reasonable to conclude that the modulation of terminal DA overflow by CCK-8S through actions at the somatodendritic region represents a form of autoregulation of these cells. Whereas CCK-8US and CCK-4 are preferential CCK-B receptor agonists, CCK-8S binds non-selectively to CCK-A and CCK-B receptors. Thus, these results implicate CCK-A receptors in the stimulatory effects of CCK-8S on VTA DA neurons.
胆囊收缩素的羧基末端八肽(CCK-8)与多巴胺(DA)共存于腹侧被盖区(VTA)的中脑边缘神经元中。在本研究中,采用自由活动大鼠体内微透析技术,评估向VTA局部注射硫酸化CCK-8(CCK-8S)、未硫酸化CCK-8(CCK-8US)和CCK四肽(CCK-4)对两个中脑边缘DA/CCK-8S终末区域(伏隔核和杏仁核)中DA溢出的相对影响。与电生理研究结果一致,注射CCK-8S而非CCK-8US或CCK-4可引起两个终末区域DA溢出增加。由于在VTA区域缺乏含CCK纤维的解剖学证据,因此可以合理推测,CCK-8S通过作用于树突-胞体区域对终末DA溢出的调节代表了这些细胞的一种自身调节形式。CCK-8US和CCK-4是CCK-B受体的优先激动剂,而CCK-8S则非选择性地与CCK-A和CCK-B受体结合。因此,这些结果表明CCK-A受体参与了CCK-8S对VTA DA神经元的刺激作用。