Motivational effects on interval timing in dopamine transporter (DAT) knockdown mice
Motivational effects on interval timing in dopamine transporter (DAT) knockdown mice
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DOI：
10.1016/j.brainres.2010.02.034
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发表时间：
2010-04-14
期刊：
影响因子：
2.9
通讯作者：
Brunner, Dani
中科院分区：
文献类型：
--
作者：
Balci, Fuat;Ludvig, Elliot A.;Brunner, Dani
我们研究了多巴胺转运蛋白（DAT）表达不足和长期细胞外多巴胺水平较高的小鼠的间隔时间（庄等人，2001）。多巴胺能系统被认为是内部时钟的神经基质，多巴胺能活性的短暂升高会产生对时间间隔的低估。采用双峰法对一组DAT敲低（KD）小鼠和一窝野生型（WT）小鼠进行检测。小鼠通过在固定的时间（30或45秒）后按压两个杠杆中的一个来获得强化。一次只有一个杠杆可用，每个杠杆与一个持续时间相关联。在偶尔的探针试验中，DAT KD小鼠在间隔时间比WT小鼠更早开始反应，但表现出最大反应和终止反应的时间与WT小鼠大致相同。给予D2拮抗剂雷氯pride（0.2、0.6和1.2 mg/kg）消除了DAT KD和WT小鼠之间的大部分差异，这表明慢性DAT下调对间隔时间的影响是由D2受体介导的。另一组DAT KD小鼠接受了视觉注意任务的训练，没有观察到缺陷，证实了时间行为的变化不是由注意介导的。我们的数据与补品多巴胺影响生物体对外部奖励信号的敏感性的观点一致，并且DAT KD小鼠奖励动机的增加降低了在计时任务中启动反应的阈值。(C) 2010 Elsevier B.V.版权所有
We examined interval timing in mice that underexpress the dopamine transporter (DAT) and have chronically higher levels of extracellular dopamine (Zhuang et al., 2001). The dopaminergic system has been proposed as a neural substrate for an internal clock, with transient elevations of dopaminergic activity producing underestimation of temporal intervals. A group of DAT knockdown (KD) and littermate wild type (WT) mice were tested with a dual peak procedure. Mice obtained reinforcement by pressing one of two levers after a fixed amount of time (30 or 45 s) had elapsed since lever extension. Only one lever was available at a time, and each lever was associated with a single duration. On occasional probe trials, the DAT KD mice began responding earlier in the interval than WT mice, but showed maximal responding and terminated responding around the same time as the WT mice. Administration of raclopride (0.2, 0.6, and 1.2 mg/kg), a D2 antagonist, eliminated most of the differences between DAT KD and WT mice, suggesting that the effects of chronic DAT downregulation on interval timing were mediated by the D2 receptors. Another cohort of DAT KD mice was trained on a visual attention task, and no deficits were observed, confirming that the changes in timed behavior were not attentionally mediated. Our data are consistent with the view that tonic dopamine affects the sensitivity of an organism to external reward signals, and that this increased motivation for reward of DAT KD mice lowers the threshold for initiating responding in a timing task. (C) 2010 Elsevier B.V. All rights reserved.