Chronic exposure to morphine, cocaine or ethanol in rats produced different effects in brain cannabinoid CB1 receptor binding and mRNA levels
Chronic exposure to morphine, cocaine or ethanol in rats produced different effects in brain cannabinoid CB1 receptor binding and mRNA levels
复制标题
大鼠长期接触吗啡、可卡因或乙醇会对大脑大麻素 CB1 受体的结合和 mRNA 水平产生不同影响
DOI：
10.1016/s0376-8716(01)00186-7
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发表时间：
2002-03-01
影响因子：
4.2
通讯作者：
Ramos, JA
中科院分区：
文献类型：
--
作者：
González, S;Fernández-Ruiz, J;Ramos, JA
最近的证据表明，内源性大麻素系统可能是大脑奖励系统的一个组成部分，然后不仅在大麻素耐受依赖中发挥作用，而且在对其他滥用药物的依赖/戒断中发挥作用。然而，很少有研究比较阿片类药物、可卡因或酒精依赖期间脑区(特别是与强化过程相关的区域)内源性大麻素配体和/或受体的变化。本研究旨在通过检测慢性吗啡暴露动物不同脑区CB1受体结合(用[H-3]-CP55.940放射自显影测量)及其mRNA水平(用原位杂交测量)的变化来达到这一目的。可卡因或乙醇。结果表明，这三种药物在CB1受体结合和mRNA水平上产生了不同的变化，这一发现排除了在对这些上瘾药物的依赖状态中存在共同的内源性大麻系统变化的可能性。因此。慢性酒精暴露通常不会改变所有被研究区域的CB1受体结合和mRNA水平。相比之下，慢性可卡因暴露只在CB1受体mRNA水平产生显著变化。下丘脑腹内侧核、大脑皮层浅层和深层转录水平下降，而海马区、运动区和边缘区无明显变化。终于来了。慢性吗啡暴露使尾壳内侧核CB1受体密度增加。但在该区域以及尾壳核外侧区和小脑中，它们的mRNA水平也降低。在边缘结构中。慢性吗啡暴露增加隔核CB受体的结合水平和mRNA水平。伏隔核内的结合也增加。但在杏仁基底外侧核减少。在海马体结构中。慢性吗啡暴露降低了齿状回中CB1受体的结合，尽管该区域的mRNA水平没有受到影响。但在亚扪人角的CA2亚区有所增加。结果表明，酒精、可卡因和吗啡的依赖机制不同，对内源性大麻素系统的影响也不同。酒精对CB1受体结合和mRNA水平没有任何影响，而可卡因只影响特定区域的转录水平，而吗啡产生不同的和区域依赖的影响。(C)2002爱思唯尔科学爱尔兰有限公司。保留所有权利。
Recent evidence suggest that the endocannabinoid system might be a component of the brain reward system and, then, play a role, not only in cannabinoid tolerance dependence, but also in dependence/withdrawal to other drugs of abuse. However, there are not many studies that compare the changes in endocannabinoid ligands and, or receptors in brain regions (particularly in those areas related to reinforcement processes) during dependence to opiates, cocaine or alcohol. The present Study addressed this objective, by examining the changes in CB1 receptor binding (measured by [H-3]-CP55.940 autoradiography) and its mRNA levels (measured by in situ hybridization) in different brain regions of animals chronically exposed to morphine. cocaine or ethanol. The results showed that these three drugs produced different changes in CB1 receptor binding and mRNA levels, a finding that precludes the existence of a common alteration of the endocannabinoid system during dependence states to these habit-Coming drugs. Thus. chronic ethanol exposure was usually uneffective in altering both CB1 receptor binding and mRNA levels in all regions examined. In contrast, chronic cocaine exposure produced significant changes only at the level of CB1 receptor mRNA. with decreases of the transcript levels in the ventromedial hypothalamic nucleus and the superficial and deep layers of the cerebral cortex, but no changes in the hippocampal, motor and limbic structures. Finally. chronic morphine exposure increased the density of CB1 receptors in the medial caudate-putamen. but decreased their mRNA levels in this region and also in the lateral caudate-putamen and the cerebellum. In limbic structures. chronic morphine exposure increased both binding and mRNA levels for CB, receptors in the septum nuclei. Binding was also increased in the nucleus accumbens. but reduced in the basolateral amygdala. In hippocampal structures. chronic morphine exposure reduced CB1 receptor binding in the dentate gyrus, although mRNA levels were unaffected in this region. but increased in the CA2 subfield of the Ammon's horn. The results indicate that mechanisms of dependence for alcohol, cocaine and morphine are different in terms of their impact on the endocannabinoid system. Alcohol did not Produce any effects on CB1 receptor binding and mRNA levels, whereas cocaine only affected transcript levels in selected regions and morphine produced divergent and region-dependent effects. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.