【摘 要】
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Introduction β-arrestin2, abundantly distributed in central nervous system, promotes endocytosis of G protein-coupled receptors and the formation of signaling complexes.However its role in neuronal fu
【机 构】
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The State Key Laboratory of Medical Neurobiology and Pharmacology Research Center;Shanghai Medical C
【出 处】
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International Conference for Physiological Sciences 2012(201
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Introduction β-arrestin2, abundantly distributed in central nervous system, promotes endocytosis of G protein-coupled receptors and the formation of signaling complexes.However its role in neuronal functions remains unclear.In the present study, we investigated the role ofβ-arrestin2 in alcohol preference.Methods Twobottle choice model used to assess alcohol-drinking behaviors and the alcohol induced conditioned place preference were tested in wild type (WT) and β-arrestin2 knockout (KO)mice.Locomotion and righting reflex tests were performed to test sensitivity of mice to ethanol.Western blot analysis and was used to detect the phosphorylation levels of enzymes and gene transcription.Results β-arrestin2 KO mice showed a marked increase in voluntary alcohol consumption without any difference in preference for saccharin or aversion to quinine, while β-arrestin2 overexpression greatly suppressed alcohol intake.Then the β-arrestin2 KO mice exhibited higher scores of conditioned place preference for alcohol.Meanwhile, the mice deficient in β-arrestin2 showed reduced sensitivity to alcohol and increased blood alcohol clearance.Furthermore, the free consumption of alcohol increased the phosphorylation level of Akt and glycogen synthase kinase 3β (GSK3β) in the dorsal striatum of wildtype (WT)mice, whereas chronic alcohol intake did not induce a further increase ofphosphorylation level of Akt in β-arrestin2KO mice which showed elevated basal levels of phosphorylated Akt and GSK3β in dorsal striatum.Conclusions These findings of our study support the notion that β-arrestin2 functions as a protective molecule to inhibit alcohol preference and reward, likely through regulating the activation of signaling pathways including Akt/GSK3β in the dorsal striatum.β-arrestin2 may thus serve as a potential target of therapies for the treatment of alcoholism.
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