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

本研究的目的是阐明脑刺激奖赏机制的神经化学基础。多巴胺（DA）是一种参与颅内自我刺激（ICSS）行为调节的神经递质。随着微透析和灵敏检测技术的发展，人们已经有可能了解递质及其代谢产物的浓度如何在行为动物大脑中特定突触区域发生变化。在第一个实验中，我们已经研究了使用这种技术是否增加细胞外DA释放的正常大鼠自发ICSS过程中发生。我们观察到内侧前脑束（MFB）的ICSS引起中脑核（NAC）中主要DA代谢物3，4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）的细胞外浓度显著增加。然而，在这些大鼠中，细胞外DA的增加较小且不显著。我们的数据 ...更多信息 e解释为表明dw ICSS增加了DA从神经末梢的释放，其被迅速吸收到末梢中，因此在正常条件下导致透析液样品中的DA浓度没有明显变化。第二个实验提供了对这种解释的支持，其中已经发现MFB的ICSS引起NAC中细胞外DA的显著增加，这可以在存在摄取抑制剂诺米芬辛的情况下证明。在第三个实验中，我们比较了DA，DOPAC和HVA的细胞外水平的变化，从三个多巴胺能终末区，内侧额叶皮层（MFC），NAC和纹状体（STR）。在诺米芬辛处理的大鼠中，MFB的ICSS引起MFB和NAC中细胞外DA水平的增加，但不引起STR中细胞外DA水平的增加。ICSS也使MFC和NAC中DOPAC和HVA的细胞外浓度以相似的程度增加，并且在STR中以较小的程度增加。结果表明，MFB的ICSS优先激活中皮质边缘DA系统，从而增加DA的释放及其在其末端区域MFC和NAC中产生的代谢。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