Wightman R M, Amatore C, Engstrom R C, Hale P D, Kristensen E W, Kuhr W G, May L J
Department of Chemistry, Indiana University, Bloomington 47405.
Neuroscience. 1988 May;25(2):513-23. doi: 10.1016/0306-4522(88)90255-2.
The rate of overflow and disappearance of dopamine from the extracellular fluid of the rat striatum has been measured during neuronal stimulation. Overflow of dopamine was induced by electrical stimulation of the medial forebrain bundle with biphasic pulse trains. The instantaneous concentration of dopamine was measured with a Nafion-coated, carbon fiber microelectrode implanted in the brain. The measurement technique, fast-scan cyclic voltammetry, samples the concentration of dopamine in less than 10 ms at 100 ms intervals. Identification of dopamine is made with cyclic voltammetry. Stimulated overflow was measured as a function of electrode position, stimulation duration, stimulation frequency, and after administration of L-DOPA and nomifensine. The observed concentration during a 2-s, 60-Hz stimulation was found to alter with position of the carbon fiber electrode. For stimuli of 3 s or less the amount of overflow was found to be a linear function of stimulus duration at a fixed electrode position. The observed overflow was found to be steady-state at a frequency of 30 Hz, suggesting a balance between uptake and synaptic overflow under these conditions. The experimental data was found to be successfully modelled when the balance of uptake and stimulated overflow was considered. It was assumed that each stimulus pulse releases a constant amount of dopamine (125 nM), and that uptake follows a Michaelis-Menten model for a single uptake site with Km = 200 nM and Vmax = 5 microM/s. The increase in stimulated overflow observed after L-DOPA (250 mg/kg) could be modelled by a 1.6-fold increase in the amount of dopamine release with no alteration of the uptake parameters. The increase in modelled by an increase in Km. In addition, the fit of the modelled data to the experimental data was improved when diffusion from the release and uptake sites was considered.
在神经元刺激过程中，已对大鼠纹状体细胞外液中多巴胺的溢出率和消失情况进行了测量。多巴胺的溢出是通过用双相脉冲串电刺激内侧前脑束诱导产生的。使用植入脑内的涂有Nafion的碳纤维微电极测量多巴胺的瞬时浓度。测量技术为快速扫描循环伏安法，以100毫秒的间隔在不到10毫秒的时间内对多巴胺浓度进行采样。通过循环伏安法鉴定多巴胺。测量了刺激溢出量与电极位置、刺激持续时间、刺激频率的函数关系，以及在给予左旋多巴和诺米芬辛后的情况。发现在2秒、60赫兹刺激期间观察到的浓度会随碳纤维电极的位置而变化。对于3秒或更短时间的刺激，发现在固定电极位置时溢出量是刺激持续时间的线性函数。发现在30赫兹频率下观察到的溢出处于稳态，这表明在这些条件下摄取和突触溢出之间达到了平衡。当考虑摄取和刺激溢出的平衡时，实验数据被成功建模。假设每个刺激脉冲释放恒定数量的多巴胺（125纳摩尔），并且摄取遵循针对单个摄取位点的米氏模型，其中Km = 200纳摩尔，Vmax = 5微摩尔/秒。左旋多巴（250毫克/千克）给药后观察到的刺激溢出增加可以通过多巴胺释放量增加1.6倍来建模，而摄取参数不变。诺米芬辛给药后观察到的溢出增加是通过Km增加来建模的。此外，当考虑从释放和摄取位点的扩散时，建模数据与实验数据的拟合得到了改善。
