The neural substrate of brain-stimulation reward : Neurochemical evidence from amicrodialysis study

本研究旨在阐明脑刺激奖赏机制的神经化学基础。多巴胺(DA)是参与调节颅内自我刺激(ICSS)行为的神经递质之一。随着微透析和灵敏检测技术的发展，已经有可能了解递质及其代谢物在行为动物大脑特定突触区域的浓度变化。在第一个实验中，我们使用这一技术研究了正常大鼠自发ICSS过程中细胞外DA释放是否增加。我们观察到内侧前脑束(MFB)的ICSS使伏核(NAC)内DA的主要代谢产物3，4-二羟基苯乙酸(DOPAC)和高香草酸(HVA)的胞外浓度显著增加。然而，在这些大鼠中，细胞外DA的增加很小，而且不明显。我们的数据是…更多的解释表明，DW ICSS增加了从神经末梢释放的DA，这些DA被迅速吸收到神经末梢，从而导致正常情况下透析液样本中的DA浓度没有明显变化。第二个实验支持这种解释，在第二个实验中，MFB的ICSS被发现导致NAC细胞外DA的显著增加，这可以在摄取抑制剂诺米芬新的存在下得到证明。在第三个实验中，我们比较了内侧额叶皮质(MFC)、内侧额叶皮质(NAC)和纹状体(STR)三个多巴胺能终末区域DA、DOPAC和HVA细胞外水平的变化。诺米芬新处理的大鼠MFB的ICSS导致MFB和NAC的细胞外多巴胺水平增加，而STR的细胞外DA水平没有增加。ICSS还增加了DOPAC和HVA在MFC和NAC中的胞外浓度，而在STR中的增加程度较小。结果表明，MFB的ICSS优先激活中皮质边缘DA系统，从而增加其终末区域MFC和NAC产生的DA释放及其代谢。较少

The purpose of this research is to elucidate the neurochemical substrates of brain-stimulation reward mechanisms. Dopamine(DA)is known to be one of the neurotransmitters involved in the mediation of intracranial self-stimulation(ICSS)behavior. With the current developments of microdialysis and sensitive detection techniques, it has been possible to understand how the concentrations of the transmitters and their metabolites change at specific synaptic regions in the brain of behaving animals. In the first experiment, we have investigated using this technique whether an increase in extracellular DA release does occur during spontaneous ICSS of normal rats. we observed that ICSS of the medial forebrain bundle(MFB)produced a marked increase in extracellular concentrations of the main DA metabolites 3, 4-dihydroxyphenylacetic acid(DOPAC)and homovanillic acid(HVA)in the nucleus accumbens(NAC). However, in these rats the increase in extracellular DA was small and not significant. Our data wer … More e interpreted as indicating dw ICSS increased the release of DA from the nerve terminals which was quickly taken up into the terminals, thus resulting in no apparent change in the DA concentrations in the dialysate samples under normal conditions. Support for this interpretation is provided by the second experiment in which ICSS of the MFB has been found to cause a pronounced increase in extracellular DA in the NAC which can be demonstrated in the presence of an uptake inhibitor, nomifensine. In the third experiment, we compared the changes in the extracellular levels of DA, DOPAC and HVA from three dopaminergic terminal regions, the medial frontal cortex(MFC), NAC and striatum(STR). ICSS of the MFB in nomifensine-treated rats caused an increase in the extracellular DA level in the MFB and NAC but not in the STR. ICSS also increased the extrasellular concentrations of DOPAC and HVA to a similar extent in the MFC and NAC and to a lesser extent in the STR. The results indicate that ICSS of the MFB preferentially activates the mesocorticolimbic DA systems, thereby increases in the release of DA and its metabolism being produced in their terminal regions, the MFC and NAC. Less