In utero ethanol experience and olfactory plasticity

子宫内乙醇体验和嗅觉可塑性

• 批准号: 7268981
• 负责人: STEVEN L. YOUNGENTOB
• 金额: $ 32.43万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7268981
• 关键词: Address; Adolescence; Adolescent; Adult; Affect; Alcohol abuse; Alcohol consumption; Alcohols; Anatomy; Animals; Behavior Control; Behavioral; Child Development; Choice Behavior; Clinical; Data; Development; Diet; Drug abuse; Environment; Epidemiologic Studies; Ethanol; Exposure to; Fetal Alcohol Exposure; Fetus; Goals; Human; Ingestion; Intake; Interdisciplinary Study; Judgment; Knowledge; Laboratories; Learning; Literature; Mediating; Memory; Nervous system structure; Odors; Olfactory Epithelium; Organism; Outcome; Pattern; Perception; Perinatal Exposure; Personal Satisfaction; Pharmaceutical Preparations; Positioning Attribute; Power stroke; Prevention approach; Preventive; Process; Range; Relative (related person); Research; Research Personnel; Resources; Risk; Sensory; Stimulus; Structure; System; Techniques; Testing; Therapeutic; Wit; Work; abstracting; age group; alcohol effect; alcohol response; base; behavior influence; clinically relevant; experience; fetal; hedonic; in utero; innovation; insight; interdisciplinary approach; mature animal; novel; olfactory bulb; postnatal; preference; prenatal; programs; relating to nervous system; response; young adult

DESCRIPTION (provided by applicant): Perhaps the best predictor of ethanol abuse in adolescence and young adult humans is prior fetal exposure to the drug. Yet, there is a relative paucity of evidence regarding the factors contributing to these long-term ingestive consequences. Studies have demonstrated that olfactory experience influences behavioral and neural sensory function; that postnatal behaviors controlled by odor stimuli are influence d by intrauterine experiences; and these experiences can be retained into adulthood, modulating intake and preference patterns. Taken together, these observations support the innovative central hypothesis of this proposal, that what the fetus learns from ethanol contamination of the prenatal environment is facilitated by a behavioral and neurophysiologic "tuning" of the olfactory system that contribute s to the later risk for preference and abuse. In support of this proposition, we provide compelling preliminary evidence that: (1) clinically relevant in utero exposure to ethanol focuses the neurophysiologic response of the olfactory system to ethanol odor at some expense to the generally broad responsivity of the system; (2) the effect was evident in the early postnatal anima l and that it persisted into adulthood; and (3) the observed neurophysiologic "tuning" to ethanol was associated wit h an alteration in the behavioral response to ethanol odor in both age groups. Thus, the long-range goal associated wit h this research program is to analyze fetal experience with ethanol in terms of its affect on an organism' s later chemosensory perception and odor-guided response to ethanol ; and to understand the mechanism s underlying the neural and behavioral effects in olfactory function related to altered odor-guided recognition and acceptance patterns of thi s drug. Guide d by our strong preliminary data, the objective of this particular application is to apply a set of interdisciplinary technique s (i.e., behavioral, neurophysiologic and anatomical) to test two specific aims: (1) we will test the hypothesis that prenatal ethanol exposure results in an altered odor-guided and drug-seeking behavioral responsiveness to ethanol that is mediated by an enhanced neurophysiologic response of the olfactory epithelium to this odorant, in both early postnatal and adult animals; and (2) we will test the hypothesis that enhanced or "tuned" olfactory bulb activation to ethanol odor and changes in specific bulbar structures mediate the experience-based alterations of the response of the olfactory periphery . The proposed research is significant, because it is expected to advance and expand our understanding of the factors contributing to the initiation of ethanol intake. An understanding of these processes will facilitate the development and testing of preventive and therapeutic strategies. It will also establish a chemosensory related conceptual framework of fetal exposure with broad based importance in child development and drug abuse.

描述（由申请人提供）：也许是青春期和年轻人滥用乙醇的最佳预测指标是先前接触该药物的胎儿。然而，关于导致这些长期摄入后果的因素的证据相对匮乏。研究表明，嗅觉经验会影响行为和神经感觉功能。由气味刺激控制的产后行为是宫内经历的影响。这些经验可以保留到成年期，调节摄入量和偏好模式。综上所述，这些观察结果支持了这一提议的创新中心假设，即胎儿从乙醇​​对产前环境的污染中学到的东西是由嗅觉系统的行为和神经生理学的“调整”促进的，从而促进了后来的偏好和滥用风险。为了支持这一主张，我们提供了令人信服的初步证据：（1）在子宫内暴露于乙醇中的临床相关性，将嗅觉系统的神经生理反应集中在乙醇气味上，以某种费用对系统的普遍响应性进行了一些费用； （2）在产后早期的动画中显而易见的效果，并且一直持续到成年； （3）观察到的神经生理学对乙醇的“调整”是在两个年龄组中对乙醇气味的行为反应的改变。因此，与该研究计划相关的远距离目标是分析乙醇对生物体后来的化学感知感和对乙醇的气味引导的反应的影响。并了解与这种药物的气味引导识别和接受模式有关的嗅觉功能中神经和行为效应的基础机制。通过我们强大的初步数据的指南D，该特定应用的目的是应用一组互律技术（即行为，神经生理学和解剖学）来测试两个具体目的：（1）我们将测试以乙醇源性和乙醇为导致的乙醇源性反应的假设，该假说是乙醇的乙醇，乙醇源性疾病，并增强了乙醇的乙醇，该乙醇是该乙醇的乙醇源性，该乙醇是该乙醇的行为，该乙醇是该假设的乙烯素化学性能，该乙醇是该假设的乙烯元素，该乙醇是该假设的乙醇源性，该乙醇是该假设的乙烯乙醇。早期和成年动物的嗅觉上皮对这种气味的反应； （2）我们将检验以下假设，即增强或“调谐”嗅球对乙醇气味的激活以及特定的鳞茎结构的变化介导了基于经验的嗅觉外围响应的改变。拟议的研究很重要，因为它有望促进和扩展我们对促成乙醇摄入启动的因素的理解。对这些过程的理解将有助于开发和测试预防和治疗策略。它还将建立与化学感应相关的胎儿暴露概念框架，其在儿童发育和药物滥用中的重要性广泛。