We sought to determine the role of functionally selective dopamine (DA) signalling pathways (G protein or β-arrestin) in DA-dependent behaviours. Mice that were globally deficient for β-arrestins or mice deficient in GSK3β in D2 receptor (D2R)-expressing neurons were used to investigate the role of functional selectivity in DA-dependent behaviours such as locomotor activity and conditioned place preference (CPP). Wild-type or knockout mice were injected with drugs such as morphine and amphetamine, which are known to increase DA levels in the brain and to induce a hyper-locomotor response and CPP. Unlike β-arrestin1 (βarr1)-deficient mice, mice globally deficient for β-arrestin2 (βarr2) mount a reduced hyperlocomotor response to either morphine or amphetamine. However, mice deficient in GSK3β in D2R-expressing neurons show a significantly reduced locomotor response to only amphetamine but not morphine. Interestingly, all mice tested show a normal CPP response to either morphine or amphetamine. β-arrestin-mediated DA receptor signalling has an important role in the locomotor response, but not CPP, to drugs such as morphine and amphetamine, demonstrating a functional selectivity of DA-dependent behaviours in mice. It is likely that G-protein-dependent signalling through DA receptors mediates the CPP response.

我们试图确定功能选择性多巴胺 (DA) 信号通路（G 蛋白或 β-arrestin）在 DA 依赖性行为中的作用。全球缺乏 β-抑制素的小鼠或表达 D2 受体 (D2R) 的神经元中缺乏 GSK3β 的小鼠被用来研究功能选择性在 DA 依赖性行为中的作用，例如运动活动和条件性位置偏好 (CPP)。给野生型或基因敲除小鼠注射吗啡和苯丙胺等药物，已知这些药物会增加大脑中的 DA 水平并诱导过度运动反应和 CPP。与缺乏 β-arrestin1 (βarr1) 的小鼠不同，全球缺乏 β-arrestin2 (βarr2) 的小鼠对吗啡或安非他明的过度运动反应降低。然而，表达 D2R 的神经元中缺乏 GSK3β 的小鼠表现出仅对苯丙胺而非吗啡的运动反应显着降低。有趣的是，所有测试的小鼠都表现出对吗啡或苯丙胺的正常 CPP 反应。β-arrestin 介导的 DA 受体信号传导在对吗啡和安非他明等药物的运动反应中具有重要作用，但在 CPP 中没有，这证明了小鼠中 DA 依赖性行为的功能选择性。通过 DA 受体的 G 蛋白依赖性信号传导可能介导 CPP 反应。证明了小鼠 DA 依赖性行为的功能选择性。通过 DA 受体的 G 蛋白依赖性信号传导可能介导 CPP 反应。证明了小鼠 DA 依赖性行为的功能选择性。通过 DA 受体的 G 蛋白依赖性信号传导可能介导 CPP 反应。