Does monoamine oxidase inhibition by pargyline increase extracellular dopamine concentrations in the striatum?
Does monoamine oxidase inhibition by pargyline increase extracellular dopamine concentrations in the striatum?
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DOI：
10.1016/0306-4522(96)00289-8
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发表时间：
1996-11-01
期刊：
影响因子：
3.3
通讯作者：
Phillips, AG
中科院分区：
文献类型：
--
作者：
Blaha, CD;Coury, A;Phillips, AG
本研究探讨了帕吉林诱导的纹状体多巴胺神经传递刺激脑内微透析测量的可能性，可能与靠近植入的微透析探针的多巴胺神经末梢的功能改变有关。多巴胺的细胞外浓度的变化，测定双侧在清醒大鼠纹状体微透析与同心透析探头和计时电流法与电化学（硬脂酸盐-石墨糊）记录电极，抑制单胺氧化酶帕吉林和随后的阻断多巴胺的摄取诺米芬新后。帕吉林（75 mg/kg，i. p.）从9 nM的平均基础值增加14 nM的多巴胺溢出，如通过植入右纹状体的透析探针所确定的。然而，帕吉林未能增加通过单独植入对侧纹状体的电化学电极测量的多巴胺基础浓度。相比之下，在帕吉林后3小时，施用诺米芬辛（10 mg/kg，i. p.）在右侧和左侧纹状体中，细胞外多巴胺浓度增加至高于基线水平的相似幅度（分别为135和127 nM）。在另一组大鼠中，将电化学电极植入左侧纹状体，电极尖端直接靠近透析探针的内腔。与帕吉林不能增加在纹状体中单独植入的电化学电极上测量的基础细胞外多巴胺相反，帕吉林给药增加了在邻近非灌注透析探针植入的电极上测量的多巴胺浓度，其程度与单独透析观察到的相似（分别为25对14 nM）。本研究表明帕吉林增加了紧邻永久植入的透析探针的轴的纹状体组织区域中的多巴胺浓度，但不在电化学电极的尖端。前一种效应似乎反映了单胺氧化酶抑制与透析探针在组织中的物理存在引起的效应之间的相互作用。版权所有（C）1996 IBRO。
The present study examined the possibility that pargyline-induced stimulation of dopamine neurotransmission in the striatum measured by intracerebral microdialysis may be related to alterations in the function of dopamine nerve terminals in close proximity to the implanted microdialysis probe. Changes in extracellular concentrations of dopamine were determined bilaterally in the striata of awake rats by microdialysis with concentric dialysis probes and by chronoamperometry with electrochemical (stearate-graphite paste) recording electrodes, after inhibition of monoamine oxidase by pargyline and subsequent blockade of dopamine uptake by nomifensine. Pargyline (75 mg/kg, i.p.) increased dopamine overflow by 14 nM from a mean basal value of 9 nM as determined from dialysis probes implanted in the right striatum. Pargyline failed, however, to increase basal concentrations of dopamine measured by electrochemical electrodes implanted alone in the contralateral striatum. In contrast, 3 h following pargyline, administration of nomifensine (10 mg/kg, i.p.) increased extracellular dopamine concentrations to a similar magnitude above baseline levels in both right and left striata (135 and 127 nM, respectively). In a separate group of rats, electrochemical electrodes were implanted in the left striatum with the tip of the electrode placed directly adjacent to the lumen of a dialysis probe. In contrast to pargyline's inability to increase basal extracellular dopamine measured at individually implanted electrochemical electrodes in the striatum, pargyline administration increased dopamine concentrations measured at electrodes implanted adjacent to non-perfused dialysis probes to an extent similar to that observed by dialysis alone (25 vs 14 nM, respectively).The present study indicates that pargyline increases dopamine concentrations in the region of striatal tissue immediately adjacent to the shaft of a permanently implanted dialysis probe, but not at the tip of an electrochemical electrode. The former effect appears to reflect an interaction between monoamine oxidase inhibition and the effects elicited by the physical presence of the dialysis probe in tissue. Copyright (C) 1996 IBRO.