Temporal characterisation of amphetamine-induced dopamine release assessed with [11C]raclopride in anaesthetised rodents
Temporal characterisation of amphetamine-induced dopamine release assessed with [11C]raclopride in anaesthetised rodents
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DOI：
10.1002/syn.10296
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发表时间：
2004-03-01
期刊：
影响因子：
2.3
通讯作者：
Grasby, PM
中科院分区：
文献类型：
--
作者：
Houston, GC;Hume, SP;Grasby, PM
内源性神经递质和放射性标记示踪剂之间的竞争，如通过正电子发射断层扫描（PET）测量的，可以提供体内内源性神经递质通量的测量。例如，碳-11标记的雷氯必利已被有效地用于监测药理学和行为操作后的多巴胺释放。本研究描述了苯丙胺诱导的[C-11]雷氯必利减少的啮齿动物模型，该模型允许表征24小时时间过程中这种减少的剂量反应和时间动力学。在研究的范围内，观察到安非他明剂量与[C-11]雷氯必利减少之间存在单调的剂量-反应关系。与先前发表的微透析数据相比，[C-11]雷氯必利结合潜力降低约16%与细胞外多巴胺增加约25倍有关。苯丙胺注射（4 mg/kg IP）后30 min观察到雷氯必利结合减少20-30%。[C-11]雷氯必利结合的这种降低持续4小时，但在8小时时恢复至基线水平。这些数据表明，持久的安非他明诱导的雷氯必利位移啮齿动物和非人灵长类动物，一个简单的竞争性占用模型可能无法充分解释的时间特性的安非他明诱导的放射性示踪剂结合的减少加强调查结果。(C)2003 Wiley-Liss，Inc.
Competition between endogenous neurotransmitters and radiolabelled tracers, as measured by positron emission tomography (PET), may provide a measure of endogenous neurotransmitter flux in vivo. For example, carbon-11 labelled raclopride has been effectively used to monitor dopamine release following pharmacological and behavioural manipulations. The current study describes a rodent model of amphetamine-induced [C-11]raclopride reduction, which allowed the characterisation of the dose-response and temporal dynamics of this reduction over a 24-h time course. Over the range studied, a monotonic dose-response relationship between amphetamine dose and [C-11]raclopride reduction was observed. When compared with previously published microdialysis data, an approximate 16% reduction in [C-11]raclopride binding potential was associated with a similar to25-fold increase in extracellular dopamine. A reduction of 20-30% in raclopride binding was observed 30 min after amphetamine injection (4 mg/kg IP). This reduction in [C-11]raclopride binding persisted for 4 h but returned to baseline by 8 h. The data suggest a persistent amphetamine-induced raclopride displacement in rodents and reinforce findings from nonhuman primates that a simple competitive occupancy model may not adequately explain the temporal characteristics of the amphetamine-induced decrease in radiotracer binding. (C) 2003 Wiley-Liss, Inc.