Acute effect of the anti-addiction drug bupropion on extracellular dopamine concentrations in the human striatum: An [11C]raclopride PET study
Acute effect of the anti-addiction drug bupropion on extracellular dopamine concentrations in the human striatum: An [11C]raclopride PET study
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DOI：
10.1016/j.neuroimage.2009.11.077
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发表时间：
2010-03-01
期刊：
影响因子：
5.7
通讯作者：
Grasby, Paul M.
中科院分区：
文献类型：
--
作者：
Egerton, Alice;Shotbolt, John P.;Grasby, Paul M.
安非他酮是一种治疗成瘾的有效药物，被广泛用作戒烟的辅助药物。安非他酮通过多巴胺转运蛋白阻断抑制纹状体多巴胺再摄取，但尚不清楚这是否会导致临床剂量下人的细胞外多巴胺水平增加。在给予生理盐水的大鼠中，使用[C-11]雷氯必利正电子发射断层扫描（PET）成像研究安非他酮对纹状体细胞外多巴胺水平的影响，11或25 mg/kg安非他酮i. p.和健康人类志愿者中施用安慰剂或150 mg安非他酮（缓释）。在人类研究中，认知任务被用来刺激多巴胺的释放。在大鼠中，安非他酮显著降低纹状体中[C-11]雷氯必利的特异性结合，与细胞外多巴胺浓度的增加一致。在人体中，未观察到纹状体[C-11]雷氯必利特异性结合显著降低。在11和25 mg/kg安非他酮i. p.的大鼠中多巴胺转运蛋白占用水平高于在所用剂量下在人中发生的预测值。因此，这些数据表明，在临床剂量下，在人体中达到的低水平多巴胺转运蛋白占有率下，安非他酮不会增加细胞外多巴胺水平。这些发现对于理解安非他酮治疗效果的作用机制以及开发成瘾和抑郁症的新治疗方法具有重要意义。(C)2009 Elsevier Inc. All rights reserved.
Bupropion is an effective medication in treating addiction and is widely used as an aid to smoking cessation. Bupropion inhibits striatal dopamine reuptake via dopamine transporter blockade, but it is unknown whether this leads to increased extracellular dopamine levels at clinical doses in man. The effects of bupropion on extracellular dopamine levels in the striatum were investigated using [C-11]raclopride positron emission tomography (PET) imaging in rats administered saline, 11 or 25 mg/kg bupropion i.p. and in healthy human volunteers administered either placebo or 150 mg bupropion (Zyban (R) Sustained-Release). A cognitive task was used to stimulate dopamine release in the human study. In rats, bupropion significantly decreased [C-11]raclopride specific binding in the striatum, consistent with increases in extracellular dopamine concentrations. In man, no significant decreases in striatal [C-11]raclopride specific binding were observed. Levels of dopamine transporter occupancy in the rat at I I and 25 mg/kg bupropion i.p. were higher than predicted to occur in man at the dose used. Thus, these data indicate that, at the low levels of dopamine transporter occupancy achieved in man at clinical doses, bupropion does not increase extracellular dopamine levels. These findings have important implications for understanding the mechanism of action underlying bupropions' therapeutic efficacy and for the development of novel treatments for addiction and depression. (C) 2009 Elsevier Inc. All rights reserved.