Alcohol exposure, social behavior and development

胎儿酒精谱系障碍（FASD）包括一系列的症状和缺陷，在社会 行为已经成为公认的可能是最衰弱的症状之一。然而，在这方面， 引起FASD中社交缺陷的行为和神经机制以及FASD的程度 环境在这些社会赤字中所起的作用仍然是未知的。因此 将改变暴露于酒精的幼崽的环境，使其暴露于密集的正常环境中。 发育期间的社会互动，少年时期的孤立，以及异常的母亲 行为，以研究减轻或加剧社会赤字的因素。相互作用 环境将在不同剂量的酒精中进行检查，预测低剂量酒精的影响 酒精的剂量对环境的影响更敏感。根据这一证据， 实验室和其他人，假设乙醇引起的社会赤字可能源于 μ阿片系统的变化。这一假设是用放射自显影和显微注射来检验的。 技术.酒精暴露动物的社会缺陷行为分析 发展表明，这些赤字不太可能是由于社会动机的变化造成的。 一些证据表明，处理社会线索的能力存在缺陷。社会 动物对不同层次的感觉线索的反应和在不同的环境中检测社会线索的能力。 将检查嗅觉、听觉和躯体感觉域。使用附加因子法， 社会线索处理缺陷对乙醇暴露人群中一般社会缺陷的贡献 动物将被确定。c-Fos免疫反应性将用于检查神经结构 导致感觉处理缺陷。本提案中使用的FASD大鼠模型需要 在产前和产后期间暴露，模仿酒精暴露的影响 在人类的三个孕期都是如此。 FASD仍然是一个公共卫生问题，对社会和公众都造成了巨大的损失。 单独的.拟议的研究将使用FASD大鼠模型来描述行为和 神经生物学机制的基础上的社会赤字在这种疾病和贡献 社会环境对乙醇在发展过程中的影响。这些发现可以 转化为FASD的生物和行为治疗。 绩效S\TE（S）（组织、城市、州） 南卡罗来纳州哥伦比亚大学心理学系 PHS 398（2004年9月修订版）第2页表格第2页 主要研究者/项目负责人（最后，第一，中间）：KELLY，Sandra，Jean 关键人员。参见说明。根据需要使用续页，以下列格式提供所需信息。 从首席研究员开始。按字母顺序列出所有其他关键人员，姓在前。 名称eRA Commons用户名组织在项目中的角色 KELLY，Sandra，J. SJKELLY南卡罗来纳州大学首席研究员 其他重要贡献者 名称组织在项目中的角色 作者：Sarah，M.南卡罗来纳州大学顾问 医学院 人胚胎干细胞（HES） 如拟进行的研究项目涉及人类胚胎干细胞，请在下列表格中列出该细胞系的注册编号 http://stemcells.nih.gov/reqistrv/index.asp.根据需要使用续页。 如果此时无法引用特定的行，请包括一个声明，说明将使用注册表中的一行。 细胞系 披露许可Sfate/nenf。仅适用于SBIR/STTR。请参阅说明。fZlYes DlMo PHS 398（09/04修订版）第2页-续表第2页-续 将下列各页依次编号 应用程序.不要使用后缀，如4a，4 b。 主要研究者/项目负责人（最后，第一，中间）：KELLY，Sandra，Jean 主要研究者/项目负责人的姓名必须在打印页和续页的顶部提供。 研究资助 目录P“e数字 首页1 说明，

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 norma 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 microinjectior 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 motivationanc 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 inthe 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. PERFORMANCE S\TE(S)(organization, city, state) Department of Psychology University of South Carolina Columbia, SC PHS 398 (Rev. 09/04) Page 2 Form Page 2 Principal Investigator/Program Director (Last, first, middle): KELLY, Sandra, Jean KEY PERSONNEL. See instructions. Use continuation pages as needed to provide the required information in the format shown below. Start with Principal Investigator. List all other key personnel in alphabetical order, last name first. Name eRA Commons User Name Organization Role on Project KELLY, Sandra,J. SJKELLY University of South Carolina PrincipalInvestigator OTHER SIGNIFICANT CONTRIBUTORS Name Organization Role on Project Sweitzer, Sarah, M. University of South Carolina Consultant School of Medicine Human Embryonic Stem Cells Bl No D Yes If the proposed project involves human embryonic stem cells, list below the registration number of the specific cell line(s) from the following lis http://stemcells.nih.gov/reqistrv/index.asp. Usecontinuation pages as needed. If a specific line cannot be referenced at this time, include a statement that one from the Registry will be used. Cell Line Disclosure Permission Sfate/nenf.Applicable to SBIR/STTR Onlv.See Instructions. fZlYes DlMo PHS 398 (Rev. 09/04) Page2-continued Form Page 2-continued Number the following pages consecutively throughout the application. Do not use suffixes such as 4a, 4b. Principal Investigator/Program Director (Last, first, middle): KELLY, Sandra, Jean The name of the principal investigator/program director must be provided at the top of each printed page and each continuation page. RESEARCH GRANT TABLE OFCONTENTS P"e Numbers Face Page 1 Description,