Chronic ethanol exposure increases peripheral-type benzodiazepine receptors in brain.

Chronic ethanol exposure increases peripheral-type benzodiazepine receptors in brain.
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慢性乙醇暴露会增加大脑中的外周型苯二氮卓受体。

DOI:
10.1016/0014-2999(88)90638-3
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发表时间:
1988
影响因子:
5
通讯作者:
Alkana,RL
Alkana,RL
中科院分区:
医学2区
文献类型:
--
作者:
Syapin,PJ;Alkana,RL

文献摘要

被引文献

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本文研究了慢性乙醇暴露、慢性乙醇暴露戒断和短期乙醇暴露对小鼠脑外周型苯二氮卓受体(PBR)和外周组织PBR的影响。雄性C57 BL/6 J小鼠在产生身体依赖性的条件下喂食含乙醇的液体饮食7.75或9天。对照小鼠接受用等热量碳水化合物代替乙醇的饮食。在暴露于乙醇7.75天的小鼠中,[3 H] Ro 5 -4864与PBR的结合在脑膜中增加,但在心脏或肾膜中没有增加。Scatchard图分析表明,增加是由于结合位点的表观数量增加,而不是受体亲和力的变化。在乙醇依赖性小鼠中获得了相同的结果,这些小鼠在结合测定之前从乙醇中退出12小时。暴露9天后,在身体依赖乙醇的小鼠中,[3 H]PK-11195与脑PBR的结合同样增加。与使用流质饮食的慢性暴露的影响相反,与盐水注射和未处理对照小鼠相比,在已知引起功能耐受的程序(3.6 g/kg i. p.,每日一次,持续4天)后重复短期暴露于乙醇未显著影响[3 H] Ro 5 -4864与脑的结合。结果与以前的研究结果是一致的,并表明,乙醇暴露导致大脑PBR的时间依赖性变化,可能与身体依赖的发展。然而,需要进一步的研究来确定酒精依赖小鼠脑PBR位点的增加是否与酒精依赖的发展有因果关系。
The effect of chronic ethanol exposure, withdrawal from chronic exposure and short-term ethanol exposure on mouse brain peripheral-type benzodiazepine receptors (PBR) and on PBR from selected peripheral tissues was studied. Male C57BL/6J mice were fed an ethanol-containing liquid diet for 7.75 or 9 days under conditions which produced physical dependence. Control mice received the diet with isocaloric carbohydrates substituted for ethanol. The binding of [3H]Ro5-4864 to PBR was increased in brain membranes, but not heart or kidney membranes, of mice exposed to ethanol for 7.75 days. Scatchard plot analysis indicated that the increase was due to an increase in the apparent number of binding sites and not to a change in receptor affinity. The same results were obtained in ethanol-dependent mice that were withdrawn from the ethanol for 12 h prior to binding determinations. The binding of [3H]PK-11195 to brain PBR was likewise increased in mice made physically dependent on ethanol after 9 days exposure. In contrast to the effects of chronic exposure using the liquid diet, repeated short-term exposure to ethanol following a procedure known to cause functional tolerance (3.6 g/kg i.p. once daily for 4 days) did not significantly affect the binding of [3H]Ro5-4864 to brain when compared to saline-injected and naive control mice. The results are consistent with previous findings and suggest that ethanol exposure causes time-dependent changes in brain PBR that may be linked to the development of physical dependence. However, further studies are necessary to determine whether the increase in brain PBR sites of alcohol-dependent mice is causally related to the development of alcohol dependence.