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脑区突触体膜对乙醇体外作用及慢性体内处理的敏感性变化。

Variations in membrane sensitivity of brain region synaptosomes to the effects of ethanol in vitro and chronic in vivo treatment.

作者信息

Gonzales R A, Ganz N, Crews F T

出版信息

J Neurochem. 1987 Jul;49(1):158-62. doi: 10.1111/j.1471-4159.1987.tb03408.x.

DOI:10.1111/j.1471-4159.1987.tb03408.x
PMID:3585327
Abstract

The effects of chronic ethanol treatment on the membrane order of synaptosomes from the cerebral cortex, striatum, cerebellum, brainstem, and hippocampus of rats were determined by measuring the fluorescence polarization of diphenylhexatriene (DPH) that had been incorporated into the synaptosomal membranes. Fischer-344 rats either were fed a nutritionally complete ethanol-containing liquid diet for 5 months or pair-fed with a diet that contained sucrose substituted isocalorically for ethanol. Polarization values for synaptosomes from all the brain regions studied were similar except for those from cerebral cortical synaptosomal membranes, which were significantly less ordered. Ethanol in vitro (30-500 mM) decreased the polarization values in synaptosomes from sucrose-control rats for all brain regions, although the sensitivity of cerebellar synaptosomes to the membrane disordering effects of ethanol in vitro was significantly greater that of synaptosomes from other brain regions. Chronic ethanol treatment did not alter baseline polarization for any brain region. Cerebellar and brainstem synaptosomes from the ethanol-fed rats were significantly less susceptible to the membrane disordering effects of ethanol in vitro compared to their sucrose controls, suggesting that chronic ethanol administration results in tolerance to ethanol's membrane effects. Striatal synaptosomes exhibited intermediate tolerance, whereas the sensitivities of cortical and hippocampal synaptosomes to membrane disordering by ethanol in vitro were not significantly affected by the chronic ethanol treatment. These results suggest that synaptosomal membranes have different membrane order requirements depending on the brain region from which they are prepared. Variations in brain regional neuronal membrane sensitivity to ethanol and differential tolerance development may contribute to some of the acute and chronic behavioral effects of ethanol.

摘要

通过测量掺入突触体膜中的二苯基己三烯(DPH)的荧光偏振,确定慢性乙醇处理对大鼠大脑皮质、纹状体、小脑、脑干和海马体突触体膜有序性的影响。Fischer-344大鼠要么喂食营养完整的含乙醇液体饲料5个月,要么与用等热量蔗糖替代乙醇的饲料进行配对喂养。除大脑皮质突触体膜的偏振值明显较低外,所有研究脑区突触体的偏振值相似。体外乙醇(30-500 mM)降低了所有脑区蔗糖对照大鼠突触体的偏振值,尽管小脑突触体对体外乙醇膜紊乱作用的敏感性明显高于其他脑区的突触体。慢性乙醇处理并未改变任何脑区的基线偏振。与蔗糖对照相比,乙醇喂养大鼠的小脑和脑干突触体对体外乙醇膜紊乱作用的敏感性明显降低,这表明慢性乙醇给药导致对乙醇膜效应的耐受性。纹状体突触体表现出中等耐受性,而慢性乙醇处理对皮质和海马体突触体在体外对乙醇膜紊乱的敏感性没有显著影响。这些结果表明,突触体膜根据其制备的脑区具有不同的膜有序性要求。脑区神经元膜对乙醇的敏感性差异和不同的耐受性发展可能导致乙醇的一些急性和慢性行为效应。

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