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αCaMKII 自身磷酸化控制酒精诱导的小鼠条件性位置偏爱形成。

αCaMKII autophosphorylation controls the establishment of alcohol-induced conditioned place preference in mice.

机构信息

MRC Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK.

出版信息

Behav Brain Res. 2013 Sep 1;252:72-6. doi: 10.1016/j.bbr.2013.05.045. Epub 2013 May 31.

Abstract

The autophosphorylation of alpha Ca2+ /calmodulin dependent protein kinase II (αCaMKII) is important for memory formation and is becoming increasingly implicated in the development of drug addiction. Previous work suggests that αCaMKII acts via the monoaminergic systems to facilitate the establishment of alcohol drinking behaviour. The present study aims to investigate whether αCaMKII autophosphorylation deficient αCaMKII(T286A) mice show a difference in the rewarding properties of alcohol (2 g/kg, i.p.), as measured by conditioned place preference (CPP). We found that alcohol-induced CPP could be established at an accelerated rate in αCaMKII(T286A) compared to wild type (WT) mice. Hyperactivity/hyper-arousal induced by the test environment was normalised by alcohol in the αCaMKII(T286A), but not WT mice. This effect could be conditioned to the test environment and may suggest enhanced negative reinforcing action of alcohol in αCaMKII autophosphorylation deficient mice.

摘要

αCa2+/钙调蛋白依赖性蛋白激酶 II(αCaMKII)的自动磷酸化对于记忆形成很重要,并且越来越多地与药物成瘾的发展有关。先前的工作表明,αCaMKII 通过单胺能系统起作用,促进酒精饮用行为的建立。本研究旨在探讨αCaMKII 自动磷酸化缺陷型αCaMKII(T286A)小鼠在酒精(2 g/kg,ip)的奖赏特性上是否存在差异,通过条件性位置偏好(CPP)进行测量。我们发现,与野生型(WT)小鼠相比,αCaMKII(T286A)小鼠可以更快地建立起酒精诱导的 CPP。在αCaMKII(T286A)小鼠中,测试环境引起的过度活动/过度唤醒被酒精正常化,但 WT 小鼠则没有。这种效应可以被条件化到测试环境中,这可能表明在αCaMKII 自动磷酸化缺陷型小鼠中,酒精的负强化作用增强。

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