β-arrestin2在可卡因诱导的奖赏行为中的作用
尹旭明, 黄冰, 马兰, 刘星
复旦大学上海医学院药理研究中心,上海 200032
摘要
β-arrestin2是G蛋白偶联受体的负反馈调控蛋白,介导受体的脱敏,此外β-arrestin2还可以通过招募信号分子,介导G蛋白非依赖的信号传导过程。β-arrestin2广泛分布于各重要脑区,参与神经环路的信号传递。本文旨在研究β-arrestin2在可卡因诱导的小鼠奖赏行为中的作用。采用β-arrestin2基因敲除小鼠(Arrb2−/−),检测了β-arrestin2在不同剂量可卡因诱导的条件性位置偏爱(conditioned place preference, CPP)形成中的作用,还检测了其在可卡因诱导的自主活动性变化中的作用。结果显示,在中等剂量(20 mg/kg)和高剂量(30 mg/kg)可卡因诱导的CPP实验中,Arrb2−/−小鼠比野生型小鼠(Arrb2+/+)表现出更强的可卡因诱导的位置偏爱,而在低剂量(10 mg/kg)可卡因实验中两者无显著性差异。可卡因诱导的Arrb2−/−小鼠的自主活动性显著低于Arrb2+/+小鼠。以上结果提示,β-arresstin2在可卡因诱导的奖赏行为中起重要作用。
关键词: β-arrestin2; 可卡因; 条件性位置偏爱; 自主活动性
分类号:R964
[β-arrestin2 plays a critical role in reward behaviors induced by cocaine.][Article in Chinese]
YIN Xu-Ming, HUANG Bing, MA Lan, LIU Xing
Pharmacology Research Center, Shanghai Medical College, Fudan University, Shanghai 200032, China
Abstract
Besides its role in desensitization and internalization of receptors, β-arrestin2 facilitates G protein-independent signaling through its ability to scaffold various signaling molecules. β-arrestin2 is widely distributed in the central nervous system, and mediates signal transduction of brain circuit. The aim of the present study was to investigate the role of β-arrestin2 in reward behaviors induced by cocaine. We assessed the conditioned place preference (CPP) induced by low (10 mg/kg), moderate (20 mg/kg) and high (30 mg/kg) doses of cocaine in Arrb2(-/-) mice and Arrb2(+/+) controls. In the Arrb2(-/-) mice, moderate and high, but not low, dose of cocaine induced pronounced increases of CPP scores, which were higher than those in the Arrb2(+/+) mice. Moreover, cocaine-induced locomotor activity was significantly lower in Arrb2(-/-) mice than that of Arrb2(+/+) littermate controls. Taken together, our results suggest a potential role of β-arrestin2 in the cocaine-induced rewarding behaviors.
Key words: β-arrestin2; cocaine; conditioned place preference; locomotor activity
收稿日期:2013-01-27 录用日期:2013-03-08
通讯作者: E-mail:
引用本文:
尹旭明, 黄冰, 马兰, 刘星. β-arrestin2在可卡因诱导的奖赏行为中的作用[J]. 生理学报 2013; 65 (2): 178-184.
YIN Xu-Ming, HUANG Bing, MA Lan, LIU Xing. [β-arrestin2 plays a critical role in reward behaviors induced by cocaine.][Article in Chinese]. Acta Physiol Sin 2013; 65 (2): 178-184 (in Chinese with English abstract).