Changes in endocannabinoid contents in the brain of rats chronically exposed to nicotine, ethanol or cocaine
Changes in endocannabinoid contents in the brain of rats chronically exposed to nicotine, ethanol or cocaine
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DOI：
10.1016/s0006-8993(02)03344-9
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发表时间：
2002-11-01
期刊：
影响因子：
2.9
通讯作者：
Ramos, JA
中科院分区：
文献类型：
--
作者：
González, S;Cascio, MG;Ramos, JA
尽管最近的数据表明，内源性大麻素的传输是大脑奖励系统的一个组成部分，并在依赖/退出不同的习惯形成药物中发挥作用，只有少数研究已经检查了内源性大麻素配体和/或受体的变化，在大脑区域与长期暴露于这些药物后的强化过程。最近，我们进行了一项比较分析大麻素CB的变化，受体密度在几个大鼠脑区域所造成的慢性暴露于一些最强大的习惯形成药物。在本研究中，我们已经扩展了这一目标，通过检查的变化，在大脑中的花生四烯酸乙醇酰胺（AEA）和2-花生四烯酸甘油（2-AG），内源性配体大麻素受体，在动物慢性暴露于可卡因，尼古丁或乙醇。结果如下。可卡因是表现出少量效应的药物，边缘前脑中2-AG含量仅少量但显著降低。与此相反，慢性酒精暴露引起中脑AEA和2-AG含量下降，而边缘前脑AEA含量增加。后一种效应在慢性尼古丁暴露后也观察到，同时脑干中AEA和2-AG含量增加。而海马、纹状体和大脑皮层的AEA和/或2-AG含量则在慢性尼古丁暴露后下降。我们还测试了慢性尼古丁对大脑CB受体的影响，这在以前没有研究过，发现这些受体的mRNA水平或结合能力几乎完全没有变化。总之，我们的研究结果与以前关于CB受体的数据一致，表明这里测试的三种药物在内源性大麻素传递中产生不同的变化。只有在酒精和尼古丁的情况下，我们观察到边缘前脑中AEA含量的共同增加。考虑到该区域是习惯形成药物的强化特性的关键区域，这一观察结果很重要，这可能支持内源性大麻素传递参与这些药物激活的奖励系统的某些特定事件。(C)2002 Elsevier Science B. V.保留所有权利。
Despite recent data suggesting that the endocannabinoid transmission is a component of the brain reward system and plays a role in dependence/withdrawal to different habit-forming drugs, only a few studies have examined changes in endocannabinoid ligands and/or receptors in brain regions related to reinforcement processes after a chronic exposure to these drugs. Recently, we carried out a comparative analysis of the changes in cannabinoid CB, receptor density in several rat brain regions caused by chronic exposure to some of the most powerful habit-forming drugs. In the present study, we have extended this objective by examining changes in the brain contents of arachidonoylethanolamide (AEA) and 2-arachidonoyl-glycerol (2-AG), the endogenous ligands for cannabinoid receptors, in animals chronically exposed to cocaine, nicotine or ethanol. Results were as follows. Cocaine was the drug exhibiting the minor number of effects, with only a small, but significant, decrease in the content of 2-AG in the limbic forebrain. In contrast, chronic alcohol exposure caused a decrease in the contents of both AEA and 2-AG in the midbrain, while it increased AEA content in the limbic forebrain. This latter effect was also observed after chronic nicotine exposure together with an increase in AEA and 2-AG contents in the brainstem. In contrast, the hippocampus, the striatum and the cerebral cortex exhibited a decrease in AEA and/or 2-AG contents after chronic nicotine exposure. We also tested the effect of chronic nicotine on brain CB, receptors, which had not been investigated before, and found an almost complete lack of changes in mRNA levels or binding capacity for these receptors. In summary, our results, in concordance with previous data on CB, receptors, indicate that the three drugs tested here produce different changes in endocannabinoid transmission. Only in the case of alcohol and nicotine, we observed a common increase in AEA contents in the limbic forebrain. This observation is important considering that this region is a key area for the reinforcing properties of habit-forming drugs, which might support the involvement of endocannabinoid transmission in some specific events of the reward system activated by these drugs. (C) 2002 Elsevier Science B.V. All rights reserved.