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慢性乙醇摄入诱导大鼠旷场行为及伏隔核中钙/钙调蛋白依赖性蛋白激酶IV表达的变化:纳洛酮的逆转作用

Chronic ethanol intake-induced changes in open-field behavior and calcium/calmodulin-dependent protein kinase IV expression in nucleus accumbens of rats: naloxone reversal.

作者信息

Li Jing, Bian Wei-liang, Xie Gui-qin, Cui Sheng-zhong, Wu Mei-ling, Li Yue-hua, Que Ling-li, Yuan Xiao-ru

机构信息

Department of Pathophysiology, Nanjing Medical University, Nanjing 210029, China.

出版信息

Acta Pharmacol Sin. 2008 Jun;29(6):646-52. doi: 10.1111/j.1745-7254.2008.00805.x.

DOI:10.1111/j.1745-7254.2008.00805.x
PMID:18501110
Abstract

AIM

To investigate the effects of chronic ethanol intake on the locomotor activity and the levels of calcium/calmodulin-dependent protein kinase IV (CaM kinase IV) in the nucleus accumbens (NAc) of rats. Simultaneously, the effects of nonselective opioid antagonist (naloxone) on the CaM kinase IV expression in the NAc and ethanol consumption of rats were also observed.

METHODS

Ethanol was administered in drinking water at the concentrations of 6% (v/v), for 28 d. The locomotor activity of rats was investigated in the open-field apparatus. CaM kinase IV levels in the NAc were analyzed using Western blotting.

RESULTS

Rats consuming ethanol solution exhibited a significant decrease of ambulation activity, accompanied by a reduced frequency of explorative rearing in an open-field task on d 7 and d 14 of chronic ethanol ingestion, whereas presumed adaptation to the neurological effects of ethanol was observed on d 28. Chronic ethanol intake elicited a significant decrease of the CaM kinase IV expression in the nuclei, but not in the cytoplasm of the NAc on d 28. Naloxone treatment significantly attenuated ethanol intake of rats and antagonized the decrease of CaM kinase IV in the nuclei of NAc neurons. The cytosolic CaM kinase IV protein levels of the NAc also increased in rats exposed to ethanol plus naloxone.

CONCLUSION

Chronic ethanol intake-induced changes in explorative behavior is mediated at least partly by changes in CaM kinase IV signaling in the nuclei of the NAc, and naloxone attenuates ethanol consumption through antagonizing the downregulation of CaM kinase IV in the NAc.

摘要

目的

研究长期摄入乙醇对大鼠运动活性及伏隔核(NAc)中钙/钙调蛋白依赖性蛋白激酶IV(CaM激酶IV)水平的影响。同时,观察非选择性阿片类拮抗剂(纳洛酮)对大鼠NAc中CaM激酶IV表达及乙醇消耗量的影响。

方法

以6%(v/v)的浓度将乙醇添加到饮用水中,持续给药28天。在旷场实验装置中研究大鼠的运动活性。采用蛋白质免疫印迹法分析NAc中CaM激酶IV的水平。

结果

饮用乙醇溶液的大鼠在慢性乙醇摄入的第7天和第14天,旷场实验中的行走活动显著减少,同时探索性竖立体位的频率降低,而在第28天观察到对乙醇神经效应的适应性。长期摄入乙醇导致在第28天NAc细胞核而非细胞质中的CaM激酶IV表达显著降低。纳洛酮治疗显著减少了大鼠的乙醇摄入量,并拮抗了NAc神经元细胞核中CaM激酶IV的降低。暴露于乙醇加纳洛酮的大鼠NAc的胞质CaM激酶IV蛋白水平也有所增加。

结论

长期摄入乙醇引起的探索行为变化至少部分由NAc细胞核中CaM激酶IV信号通路的变化介导,纳洛酮通过拮抗NAc中CaM激酶IV的下调来减少乙醇消耗。

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