Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Eur J Neurosci. 2013 Jun;37(11):1779-88. doi: 10.1111/ejn.12191. Epub 2013 Mar 20.
Variation in dopamine receptor levels has been associated with different facets of impulsivity. To further delineate the neural substrates underlying impulsive action (inability to withhold a prepotent motor response) and impulsive choice (delay aversion), we characterised rats in the Differential Reinforcement of Low Rates of Responding task and a delay discounting task. We also measured performance on an effort-based discounting task. We then assessed D1 and D2 dopamine receptor mRNA expression in subregions of the prefrontal cortex and nucleus accumbens using in situ hybridisation, and compared these data with behavioral performance. Expression of D1 and D2 receptor mRNA in distinct brain regions was predictive of impulsive action. A dissociation within the nucleus accumbens was observed between subregions and receptor subtypes; higher D1 mRNA expression in the shell predicted greater impulsive action, whereas lower D2 mRNA expression in the core predicted greater impulsive action. We also observed a negative correlation between impulsive action and D2 mRNA expression in the prelimbic cortex. Interestingly, a similar relationship was present between impulsive choice and prelimbic cortex D2 mRNA, despite the fact that behavioral indices of impulsive action and impulsive choice were uncorrelated. Finally, we found that both high D1 mRNA expression in the insular cortex and low D2 mRNA expression in the infralimbic cortex were associated with willingness to exert effort for rewards. Notably, dopamine receptor mRNA in these regions was not associated with either facet of impulsivity. The data presented here provide novel molecular and neuroanatomical distinctions between different forms of impulsivity, as well as effort-based decision-making.
多巴胺受体水平的变化与冲动的不同方面有关。为了进一步描绘冲动行为（无法抑制优势运动反应）和冲动选择（延迟厌恶）的神经基础，我们在低反应率强化任务和延迟折扣任务中对大鼠进行了特征描述。我们还在基于努力的折扣任务上测量了性能。然后，我们使用原位杂交技术评估了前额叶皮层和伏隔核的不同脑区中的 D1 和 D2 多巴胺受体 mRNA 表达，并将这些数据与行为表现进行了比较。不同脑区中 D1 和 D2 受体 mRNA 的表达可预测冲动行为。在伏隔核中观察到不同的亚区和受体亚型之间的分离；壳中的 D1 mRNA 表达较高预测冲动行为更大，而核心中的 D2 mRNA 表达较低预测冲动行为更大。我们还观察到冲动行为与前额叶皮层 D2 mRNA 之间存在负相关。有趣的是，尽管冲动行为和冲动选择的行为指标不相关，但在冲动选择和前额叶皮层 D2 mRNA 之间存在类似的关系。最后，我们发现岛叶皮层中 D1 mRNA 表达较高和下边缘皮层中 D2 mRNA 表达较低与为奖励付出努力的意愿有关。值得注意的是，这些区域中的多巴胺受体 mRNA 与冲动的任何方面都没有关联。这里呈现的数据为不同形式的冲动以及基于努力的决策提供了新颖的分子和神经解剖学区别。
