In utero ethanol experience and olfactory plasticity

子宫内乙醇体验和嗅觉可塑性

基本信息

批准号：
8119253
负责人：
STEVEN L. YOUNGENTOB
金额：
$ 13.91万
依托单位：
UPSTATE MEDICAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-10 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8119253
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 Pharmaceutical Preparations Positioning Attribute Power stroke Prevention approach Preventive Process 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

项目摘要

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）：也许青春期和年轻成年人中乙醇滥用的最佳预测因素是胎儿之前接触过该药物。然而，关于导致这些长期摄入后果的因素的证据相对较少。研究表明嗅觉体验影响行为和神经感觉功能；由气味刺激控制的产后行为受到宫内经历的影响；这些经历可以保留到成年，从而调节摄入量和偏好模式。总而言之，这些观察结果支持了该提案的创新中心假设，即胎儿从产前环境的乙醇污染中学到的东西是通过嗅觉系统的行为和神经生理学“调整”促进的，这有助于后来的偏好和偏好风险。虐待。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的临床相关性集中于嗅觉系统对乙醇气味的神经生理反应，但牺牲了系统普遍广泛的响应性； (2) 这种效应在动物出生后早期就很明显，并且持续到成年期； (3)观察到的对乙醇的神经生理学“调节”与两个年龄组对乙醇气味的行为反应的改变有关。因此，与该研究计划相关的长期目标是分析胎儿对乙醇的体验，了解其对有机体后来的化学感觉感知和对乙醇的气味引导反应的影响；并了解与该药物的气味引导识别和接受模式改变相关的嗅觉功能神经和行为影响的潜在机制。在我们强有力的初步数据的指导下，这一特定应用的目标是应用一套跨学科技术（即行为、神经生理学和解剖学）来测试两个特定目标：（1）我们将测试产前乙醇暴露的假设在出生后早期和成年动物中，导致对乙醇的气味引导和药物寻求行为反应发生改变，这是由嗅觉上皮对这种气味剂的神经生理反应增强介导的； (2)我们将检验以下假设：增强或“调节”嗅球对乙醇气味的激活以及特定球结构的变化介导基于经验的嗅觉周围反应的改变。拟议的研究意义重大，因为它有望推进和扩大我们对导致乙醇摄入的因素的理解。了解这些过程将有助于预防和治疗策略的开发和测试。它还将建立一个与化学感应相关的胎儿暴露概念框架，在儿童发育和药物滥用方面具有广泛的重要性。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Gestational ethanol exposure alters the behavioral response to ethanol odor and the expression of neurotransmission genes in the olfactory bulb of adolescent rats.

妊娠期乙醇暴露改变了青春期大鼠对乙醇气味的行为反应和嗅球神经传递基因的表达。

DOI：
发表时间：
2009-02-03
期刊：
影响因子：
2.9
作者：
Middleton, Frank A;Carrierfenster, Kellyn;Mooney, Sandra M;Youngentob, Steven L
通讯作者：
Youngentob, Steven L

The effect of gestational ethanol exposure on voluntary ethanol intake in early postnatal and adult rats.

妊娠期乙醇暴露对产后早期和成年大鼠自愿乙醇摄入的影响。

DOI：
发表时间：
2007-12
期刊：
影响因子：
1.9
作者：
Youngentob, Steven L;Molina, Juan C;Spear, Norman E;Youngentob, Lisa M
通讯作者：
Youngentob, Lisa M

Experience-induced fetal plasticity: the effect of gestational ethanol exposure on the behavioral and neurophysiologic olfactory response to ethanol odor in early postnatal and adult rats.

经验诱发的胎儿可塑性：妊娠期乙醇暴露对产后早期和成年大鼠对乙醇气味的行为和神经生理嗅觉反应的影响。

DOI：
发表时间：
2007-12
期刊：
影响因子：
1.9
作者：
Youngentob, Steven L;Kent, Paul F;Sheehe, Paul R;Molina, Juan C;Spear, Norman E;Youngentob, Lisa M
通讯作者：
Youngentob, Lisa M

The relationship between PROP and ethanol preferences: an evaluation of 4 inbred mouse strains.

PROP 和乙醇偏好之间的关系：对 4 个近交系小鼠品系的评估。