You Z B, Tzschentke T M, Brodin E, Wise R A
Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montreal, Quebec, Canada H3G 1M8.
J Neurosci. 1998 Aug 15;18(16):6492-500. doi: 10.1523/JNEUROSCI.18-16-06492.1998.
In vivo microdialysis, radioimmunoassay, and HPLC with electrochemical or fluorometric detection were used to investigate the release of cholecystokinin (CCK), glutamate (Glu), and dopamine (DA) in nucleus accumbens septi (NAS) as a function of ipsilateral electrical stimulation of medial prefrontal cortex (mPFC). CCK was progressively elevated by mPFC stimulation at 50-200 Hz. Stimulation-induced CCK release was intensity-dependent at 250-700 microA. NAS Glu and DA levels were each elevated by stimulation at 25-400 Hz; the dopamine metabolites DOPAC and homovanillic acid were increased by stimulation at 100-400 Hz. When rats were trained to lever press for mPFC stimulation, the stimulation induced similar elevations of each of the three transmitters to those seen with experimenter-administered stimulation. Perfusion of 1 mM kynurenic acid (Kyn) into either the ventral tegmental area (VTA) or NAS blocked lever pressing for mPFC stimulation. VTA, but not NAS, perfusion of Kyn significantly attenuated the increases in NAS DA levels induced by mPFC stimulation. Kyn did not affect NAS CCK or Glu levels when perfused into either the VTA or NAS. The present results are consistent with histochemical evidence and provide the first in vivo evidence for the existence of a releasable pool of CCK in the NAS originating from the mPFC. Although dopamine is the transmitter most closely linked to reward function, it was CCK that showed frequency-dependent differences in release corresponding most closely to rewarding efficacy of the stimulation. Although not essential for the reward signal itself, coreleased CCK may modulate the impact of the glutamatergic action in this behavior.
采用体内微透析、放射免疫分析以及带有电化学或荧光检测的高效液相色谱法，研究伏隔核（NAS）中胆囊收缩素（CCK）、谷氨酸（Glu）和多巴胺（DA）的释放情况，作为内侧前额叶皮质（mPFC）同侧电刺激的函数。在50 - 200 Hz频率下，mPFC刺激使CCK逐渐升高。在250 - 700微安时，刺激诱导的CCK释放呈强度依赖性。在25 - 400 Hz频率下，刺激使NAS中的Glu和DA水平均升高；在100 - 400 Hz频率下，刺激使多巴胺代谢产物3,4-二羟基苯乙酸（DOPAC）和高香草酸升高。当大鼠经训练通过按压杠杆来接受mPFC刺激时，该刺激诱导的三种递质的升高与实验者给予刺激时所见相似。向腹侧被盖区（VTA）或NAS灌注1 mM犬尿氨酸（Kyn）可阻断为接受mPFC刺激而进行的杠杆按压。向VTA而非NAS灌注Kyn可显著减弱mPFC刺激诱导的NAS中DA水平的升高。当向VTA或NAS灌注Kyn时，Kyn不影响NAS中的CCK或Glu水平。目前的结果与组织化学证据一致，并首次提供了体内证据，证明NAS中存在源自mPFC的可释放CCK池。尽管多巴胺是与奖赏功能联系最紧密的递质，但显示出释放频率依赖性差异且与刺激奖赏效力最密切对应的是CCK。虽然共释放的CCK对奖赏信号本身并非必不可少，但它可能会调节这种行为中谷氨酸能作用的影响。
