摘要
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.
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.
基金
supported by the National Basic Research Development Program of Ministry of Science and Technology, China (2009CB522006)
the National Natural Science Foundation of China (30901798, 91232307 and 31121061)
