Domain-dependent effects of DAT inhibition in the rat dorsal striatum.

Domain-dependent effects of DAT inhibition in the rat dorsal striatum.
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DOI:
10.1111/j.1471-4159.2012.07774.x
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发表时间:
2012-07
影响因子:
4.7
通讯作者:
Michael AC
Michael AC
中科院分区:
医学2区
文献类型:
--
作者:
Mitch Taylor I;Jaquins-Gerstl A;Sesack SR;Michael AC

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大鼠背纹状体表现出多巴胺释放和清除的域依赖动力学。本报告描述了竞争性多巴胺摄取抑制剂诺米芬(20mg /kg i.p.)在电刺激内侧前脑束时通过伏安法记录的多巴胺诱发反应的结构域依赖性作用。在慢域,诺米芬增加了诱发溢出的初始速率,增加了反应超调,不影响多巴胺清除曲线线性部分的斜率,而减缓了清除曲线非线性部分的斜率。在快速区域,诺米芬不影响溢出的初始速率,增加刺激结束超调,并降低多巴胺清除曲线线性段的斜率。总的来说,这些发现与现有的多巴胺诱发释放模型不一致,这些模型将诺米芬的作用描述为增加多巴胺摄取的有效KM。这些发现表明,诱发释放后的多巴胺清除受多巴胺摄取和受限的细胞外扩散过程的影响。
The rat dorsal striatum exhibits domain-dependent kinetics of dopamine release and clearance. The present report describes the domain-dependent actions of nomifensine (20 mg/kg i.p.), a competitive dopamine uptake inhibitor, on evoked dopamine responses recorded by voltammetry during electrical stimulation of the medial forebrain bundle. In slow domains, nomifensine increases the initial rate of evoked overflow, increases response overshoot, does not affect the slope of the linear segment of the dopamine clearance profile, and slows the non-linear segment of the clearance profile. In fast domains, nomifensine does not affect the initial rate of overflow, increases the end-of-stimulus overshoot, and decreases the slope of the linear segment of the dopamine clearance profile. Collectively, these findings do not concur with existing models of evoked dopamine release that describe the effect of nomifensine as an increase in the effective KM of dopamine uptake. These findings suggest that dopamine clearance after evoked release is affected by both dopamine uptake and a restricted extracellular diffusion process.
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