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D-2拮抗剂对伏隔核和尾状核-壳核中频率依赖性刺激的多巴胺释放的影响。

Effects of D-2 antagonists on frequency-dependent stimulated dopamine overflow in nucleus accumbens and caudate-putamen.

作者信息

May L J, Wightman R M

机构信息

Department of Chemistry, Indiana University, Bloomington.

出版信息

J Neurochem. 1989 Sep;53(3):898-906. doi: 10.1111/j.1471-4159.1989.tb11789.x.

DOI:10.1111/j.1471-4159.1989.tb11789.x
PMID:2527290
Abstract

Stimulated dopamine overflow has been measured with in vivo voltammetry in the caudate-putamen and nucleus accumbens. Overflow was induced by electrical stimulation of the medial forebrain bundle with 120 1-ms, 300-microA, biphasic pulses at frequencies between 10 and 60 Hz. Overflow was measured with a Nafion-coated, carbon-fiber electrode used with fast-scan voltammetry (300 V s-1). Quantification and identification of dopamine concentrations down to 100 nM in vivo is possible with this technique. The overflow curves were fit to a kinetic model that describes the measured response as a function of uptake (characterized by a Vmax and Km) and release (characterized by the concentration of dopamine released per stimulus pulse). Overflow curves in both regions could be described with similar kinetic parameters except for the Vmax, which in the nucleus accumbens was only 60% of that measured in the caudate-putamen. Uptake inhibition by nomifensine (20 mg kg-1) caused an apparent 15-fold change in the value of Km in the nucleus accumbens, similar to results previously reported in the caudate-putamen. In contrast, metoclopramide (10 mg kg-1) and sulpiride (100 mg kg-1) altered the apparent amount of dopamine released per stimulus pulse without a change in the uptake kinetics.

摘要

已通过体内伏安法测量了尾状核 - 壳核和伏隔核中刺激引起的多巴胺溢出。通过以120个1毫秒、300微安的双相脉冲,频率在10至60赫兹之间电刺激内侧前脑束来诱导溢出。使用与快速扫描伏安法(300伏/秒)一起使用的涂有Nafion的碳纤维电极测量溢出。使用该技术可以在体内定量和鉴定低至100纳摩尔的多巴胺浓度。溢出曲线拟合到一个动力学模型,该模型将测量的响应描述为摄取(以Vmax和Km表征)和释放(以每个刺激脉冲释放的多巴胺浓度表征)的函数。除了Vmax外,两个区域的溢出曲线都可以用相似的动力学参数来描述,其中伏隔核中的Vmax仅为尾状核 - 壳核中测量值的60%。诺米芬辛(20毫克/千克)的摄取抑制导致伏隔核中Km值出现明显的15倍变化,这与先前在尾状核 - 壳核中报道的结果相似。相比之下,甲氧氯普胺(10毫克/千克)和舒必利(100毫克/千克)改变了每个刺激脉冲释放的多巴胺表观量,而摄取动力学没有变化。

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