Alcohol exposure, social behavior and development

描述（由申请人提供）：胎儿酒精谱系障碍（FASD）包括一系列症状，社会行为缺陷已被公认为可能是最虚弱的症状之一。然而，引起FASD中所见社会缺陷的行为和神经机制以及环境在这些社会缺陷中所起作用的程度仍不清楚。因此，暴露于酒精的幼崽的环境将被改变，使它们在发育期间暴露于密集的正常社会互动中，在幼年期被隔离，以及异常的母性行为，以检查减轻或加剧社会缺陷的因素。环境的相互作用将在不同剂量的酒精中进行检查，并预测低剂量酒精的影响将对环境操纵更敏感。根据本实验室和其他实验室的证据，我们假设酒精引起的社会缺陷可能是由mu阿片系统的变化引起的。利用放射自显影和显微注射技术对这一假设进行了检验。对在发育过程中接触酒精的动物所观察到的社会缺陷的行为分析表明，这些缺陷不太可能是由于社会动机的改变，一些证据表明，处理社会线索的能力存在缺陷。动物对不同层次的感觉线索的社会反应以及在嗅觉、听觉和体感领域检测社会线索的能力将被检查。利用加性因子法，确定了酒精暴露动物社会线索加工缺陷对社会缺陷的贡献。c-Fos免疫反应性将用于检查导致感觉加工缺陷的神经结构。本提案中使用的FASD大鼠模型需要在产前和产后期间暴露，模仿人类在所有三个月期间暴露于酒精的影响。FASD仍然是一个公共卫生问题，对社会和个人都造成了巨大的损失。该研究将使用大鼠FASD模型来描述这种疾病中社会缺陷的行为和神经生物学机制，以及社会环境对乙醇在发育过程中的影响的贡献。这些发现可以转化为FASD的生物学和行为治疗。

DESCRIPTION (provided by applicant): Fetal alcohol spectrum disorder (FASD) includes a constellation of symptoms and deficits in social behavior has become acknowledged as possibly one of the most debilitating symptoms. However, the behavioral and neural mechanism giving rise to the social deficits seen in FASD and the degree to which the environment plays a role in these social deficits remains unknown. Thus, the environment of alcohol-exposed pups will be modified such that they are exposed to intensive normal social interactions during development, isolation during the juvenile period, and abnormal mothering behavior in order to examine mitigating or exacerbating factors in the social deficits. Interactions of environment will be examined across different doses of alcohol, with the prediction that effects of low doses of alcohol will be more sensitive to environmental manipulations. Based on evidence from this laboratory and others, it is hypothesized that the ethanol-induced social deficits might arise from changes in mu opioid system. This hypothesis is examined using autoradiography and microinjection techniques. Behavioral analyses of the social deficits observed in animals exposed to alcohol during development has demonstrated that the deficits are not likely due to changes in social motivation and some evidence suggests that there are deficits in the ability to process social cues. The social response of animals to different gradations of sensory cues and the ability to detect social cues in the olfactory, auditory and somatosensory domains will be examined. Using the additive factors method, the contribution of deficits in social cue processing to social deficits in general in ethanol-exposed animals will be determined. c-Fos immunoreactivity will be used to examine the neural structures contributing to the sensory processing deficit. The rat model of FASD used in this proposal entails exposure during both the prenatal and postnatal period, mimicking the effect of alcohol exposure during all three trimesters in the humans. FASD continues to be a public health problem occurring large expenses both to society and the individual. The proposed studies will use a rat model of FASD to delineate the behavioral and neurobiological mechanism underlying the social deficits in this disorder and the contribution of social environments to the impact of ethanol during development. These findings can then be translated into both biological and behavioral treatments for FASD.