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酒精成瘾易感性大鼠边缘系统代谢减少和额皮质体积减小。

Reduced limbic metabolism and fronto-cortical volume in rats vulnerable to alcohol addiction.

机构信息

Istituto Italiano di Tecnologia, Center for Nanotechnology Innovation, Pisa, & Center for Neuroscience and Cognitive Systems at UniTn, Rovereto, Italy.

出版信息

Neuroimage. 2013 Apr 1;69:112-9. doi: 10.1016/j.neuroimage.2012.12.015. Epub 2012 Dec 20.

Abstract

Alcohol abuse is associated with long-term reductions in fronto-cortical volume and limbic metabolism. However, an unanswered question in alcohol research is whether these alterations are the sole consequence of chronic alcohol use, or contain heritable contributions reflecting biological propensity toward ethanol addiction. Animal models of genetic predisposition to alcohol dependence can be used to investigate the role of inborn brain abnormalities in the aetiology of alcoholism. Here we used magnetic resonance imaging (MRI) in the Marchigian-Sardinian (msP) alcohol-preferring rats to assess the presence of inherited structural or functional brain alterations. Alcohol-naïve msP (N=22) and control rats (N=26) were subjected to basal cerebral blood volume (bCBV) mapping followed by voxel-based morphometry (VBM) of grey matter and tract-based spatial statistics mapping of white matter fractional anisotropy. msP rats exhibited significantly reduced bCBV, an established marker of resting brain function, in focal cortico-limbic and thalamic areas, together with reduced grey matter volume in the thalamus, ventral tegmental area, insular and cingulate cortex. No statistically significant differences in fractional anisotropy were observed between groups. These findings highlight the presence of inborn grey matter and metabolic abnormalities in alcohol-naïve msP rats, the localization and sign of which are remarkably similar to those mapped in abstinent alcoholics and subjects at high risk for alcohol dependence. Collectively, these results point for a significant role of heritable neurofunctional brain alterations in biological propensity toward ethanol addiction, and support the translational use of advanced imaging methods to describe the circuital determinants of vulnerability to drug addiction.

摘要

酗酒与额皮质体积和边缘代谢的长期减少有关。然而,酒精研究中一个未解决的问题是,这些改变是慢性酒精使用的唯一后果,还是包含反映对乙醇成瘾的生物倾向的遗传贡献。对酒精依赖遗传易感性的动物模型可用于研究内在大脑异常在酒精中毒发病机制中的作用。在这里,我们使用磁共振成像(MRI)在三月吉亚-撒丁岛(msP)酒精偏好大鼠中评估遗传结构或功能脑改变的存在。未接触酒精的 msP(N=22)和对照大鼠(N=26)接受基础脑血容量(bCBV)映射,然后进行灰质基于体素的形态测量学(VBM)和白质各向异性分数基于体素的空间统计学映射。msP 大鼠表现出明显的皮质-边缘和丘脑区域的 bCBV 降低,这是静息脑功能的既定标志物,以及丘脑、腹侧被盖区、岛叶和扣带回皮质的灰质体积减少。两组之间的各向异性分数没有统计学上的显著差异。这些发现强调了未接触酒精的 msP 大鼠中存在内在的灰质和代谢异常,其定位和特征与在戒酒的酗酒者和酒精依赖高风险的个体中映射的非常相似。总的来说,这些结果表明遗传神经功能大脑改变在对乙醇成瘾的生物倾向中起重要作用,并支持使用先进的成像方法来描述对药物成瘾的易感性的回路决定因素。

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