Heien M L A V, Wightman R M
Department of Chemistry and Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599-3290, USA.
CNS Neurol Disord Drug Targets. 2006 Feb;5(1):99-108. doi: 10.2174/187152706784111605.
The neurotransmitter dopamine is important in reward processing, however its precise modulatory role is still being investigated. Carbon-fiber microelectrodes can be used to monitor dopamine on a subsecond time scale in the striatum and nucleus accumbens of rats during behavior, and this approach is providing new insights into the mechanisms that control its extracellular concentration as well as the conditions under which it is released. Three main processes govern the amount of dopamine measured extrasynaptically: exocytotic release, neuronal uptake, and diffusion away from the release site. By monitoring local extracellular dopamine concentrations in the striatum following electrical stimulation of dopamine-containing neurons, release, uptake and diffusion can be individually examined and quantified. Dopaminergic neurons have been shown to fire in two firing modes, tonic and bursts at higher frequency. Electrical stimulation can be designed to mimic either mode to examine their effects on dopamine release. Burst firing causes a transient increase in extracellular dopamine while tonic firing causes a new steady-state level. In behaving primates, dopaminergic neurons display short-latency, phasic firing to primary reward and conditioned cues associated with reward. These bursts code differences between actual and predicted rewards. In rats, transient dopamine release in terminal regions that mimics that seen during burst firing has been demonstrated during reward-related cues. Taken together, these studies indicate that phasic dopamine release is a critical mediator of reward-related processes.
神经递质多巴胺在奖赏处理过程中起着重要作用，然而其确切的调节作用仍在研究之中。碳纤维微电极可用于在行为过程中以亚秒级时间尺度监测大鼠纹状体和伏隔核中的多巴胺，这种方法为控制其细胞外浓度的机制以及其释放的条件提供了新的见解。有三个主要过程决定了突触外测得的多巴胺量：胞吐释放、神经元摄取以及从释放位点扩散。通过监测电刺激含多巴胺神经元后纹状体中的局部细胞外多巴胺浓度，可以分别检测和量化释放、摄取及扩散情况。多巴胺能神经元已被证明以两种放电模式放电，即低频紧张性放电和高频爆发式放电。电刺激可设计为模拟这两种模式中的任何一种，以研究它们对多巴胺释放的影响。爆发式放电会导致细胞外多巴胺短暂增加，而紧张性放电会导致新的稳态水平。在行为中的灵长类动物中，多巴胺能神经元对初级奖赏以及与奖赏相关的条件线索会表现出短潜伏期的相位性放电。这些爆发式放电编码了实际奖赏与预期奖赏之间的差异。在大鼠中，已证实在与奖赏相关的线索出现时，其终末区域会出现类似于爆发式放电期间所见的短暂多巴胺释放。综上所述，这些研究表明相位性多巴胺释放是奖赏相关过程的关键调节因子。
