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(20mg/kg)和高剂量(30mg/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(10mg/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。
In this study,we investigated the role ofβ-arrestin-2in alcohol preference using the two-bottle choice and conditioned place preference procedures in wild-type（WT）andβ-arrestin-2 knockout（KO）mice.Locomotion and righting reflex tests were performed to test alcohol sensitivity.The possible molecular signals regulated byβ-arrestin-2 were analyzed by Western blot.We found thatβ-arrestin-2 KO mice showed a marked increase in voluntary alcohol consumption without significant differences in preference for saccharin or aversion to quinine.These animals also exhibited higher conditioned place preference scores for alcohol than WT mice.Meanwhile,KO mice showed reduced sensitivity to alcohol and increased blood alcohol clearance.Furthermore,after the free consumption of alcohol,the activities of protein kinase B and glycogen synthase kinase 3β（GSK3β）increased in the dorsal striatum of WT mice,but not in KO mice,which showed high basal activity of Akt in the dorsal striatum.These results suggest thatβ-arrestin-2 negatively regulates alcohol preference and reward,likely through regulating the activation of signaling pathways including Akt/GSK3βin the dorsal striatum.
