Alcohol exposure, social behavior and development

描述（由申请人提供）：胎儿酒精谱系障碍（FASD）包括一系列症状和社会行为缺陷，已被公认为可能是最令人衰弱的症状之一。然而，引起FASD中所见的社会缺陷的行为和神经机制以及环境在这些社会缺陷中发挥作用的程度仍然未知。因此，将改变暴露于酒精的幼崽的环境，使其在发育期间暴露于密集的正常社会互动，在青少年时期暴露于隔离，以及异常的母性行为，以检查社会缺陷的缓解或加剧因素。环境的相互作用将在不同剂量的酒精中进行研究，预测低剂量酒精的影响将对环境操纵更加敏感。基于本实验室和其他实验室的证据，推测乙醇诱导的社交缺陷可能是由于μ阿片系统的变化。这一假设是检查使用放射自显影和显微注射技术。在发育过程中暴露于酒精的动物中观察到的社会缺陷的行为分析表明，赤字不太可能是由于社会动机的变化，一些证据表明，有缺陷的能力处理社会线索。动物的社会反应不同层次的感官线索和能力，以检测社会线索的嗅觉，听觉和体感域将进行检查。使用加性因子法，将确定乙醇暴露动物中社交线索处理缺陷对一般社交缺陷的贡献。c-Fos免疫反应性将用于检查导致感觉处理缺陷的神经结构。本提案中使用的FASD大鼠模型需要在产前和产后期间暴露，模拟人类所有三个孕期的酒精暴露影响。FASD仍然是一个公共卫生问题，给社会和个人带来巨大损失。拟议的研究将使用FASD大鼠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.