INTEGRATIVE NEUROSCIENCE INITIATIVE ON ALCOHOLISM (INIA)

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。目的：使用酒精偏好大鼠（p -大鼠）的体内定量神经成像，酒精中毒的动物模型，检查酒精暴露的纵向影响，同时控制随年龄增长而发生的形态学变化。方法：对两组成年p -大鼠进行纵向设计，获得结构MRI。每个队列中的一些人从未接触过酒精，而另一些人则接受酒精：三瓶选择，分别为0%，15%（或20%）和30%（或40%）几种不同的暴露方案：连续暴露；周期为两周，然后两周戒酒；在黑暗中狂饮会导致大量饮酒。在大鼠大约3、6、10、13、15和19个月时重复扫描。结果：非酒精暴露大鼠的全脑容量在15个月左右达到最大水平，而体重继续增加，无渐近线。在测量的大脑结构中，生长并不均匀。在研究的最初12个月里，胼胝体面积扩大了36%，小脑扩大了17%，海马体扩大了10%；虽然心室增大了21%，但由于受试者之间存在很大的差异，这种影响并不显著。影响生长率估计的因素包括凋落物效应、MR图像信噪比和测量误差。与纵向人类报告的老化脑组织区域体积下降不同，成年大鼠的几个大脑结构继续增长。暴露在酒精中的大鼠也显示出大脑的生长，但这种生长减弱了，尤其是在胼胝体中。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aims: Use in vivo quantitative neuroimaging of alcohol-preferring rat (P-rat), an animal model of alcoholism, to examine longitudinal effects of alcohol exposure, while controlling for morphological changes that occur with age. Methods: Structural MRI was acquired in a longitudinal design on two cohorts of adult P-rats. Some of each cohort were never exposed to alcohol, while others received alcohol: a three-bottle choice with 0%, 15% (or 20%), and 30 % (or 40%) several different exposure schemes: continuous exposure; cycles of 2 weeks on followed by 2 weeks off alcohol; and binge drinking in the dark leading to high levels of alcohol consumption. Scanning was repeated when rats were approximately 3, 6, 10, 13, 15, and 19 months. Results: The non-alcohol exposed rats showed growth in whole brain volume that reached maximal levels by about 15 months, whereas body weight continued its gain without asymptote. Growth was not uniform across brain structures measured. Over the initial 12 months of the study, corpus callosum area expanded 36%, cerebellum 17%, and hippocampus 10%; although the ventricles enlarged 21%, the effect was not significant because of substantial between-subject variance. Factors affecting growth rate estimates included litter effects, MR image signal-to-noise ratio, and measurement error. Unlike longitudinal human reports of regional volume declines in aging brain tissue, several brain structures in adult rats continued growing. The alcohol-exposed rats also showed brain growth but this was attenuated, particularly in the corpus callosum.