Ethanol Exposure & The Role of Chemosensory Plasticity in EtOH Acceptance

乙醇暴露

• 批准号: 9323205
• 负责人: STEVEN L. YOUNGENTOB
• 金额: $ 23.06万
• 依托单位: STATE UNIVERSITY OF NY,BINGHAMTON
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9323205
• 关键词: Address; Adolescence; Adolescent; Adult; Age; Alcohol abuse; Alcohol consumption; Alcohols; Animals; Avidity; Behavior; Behavioral; Cell physiology; Consumption; Data; Development; Environmental Exposure; Epigenetic Process; Ethanol; Fetal Alcohol Exposure; Fetus; Gene Expression; Gene Expression Profile; Genes; Glossopharyngeal nerve structure; Goals; Growth; Human; Ingestion; Intake; Irritants; Knowledge; Literature; Maps; Mediating; Methods; Nerve; Neurophysiology - biologic function; Odors; Pattern; Perception; Peripheral; Publishing; Quantitative Trait Loci; Quinine; Rattus; Receptor Gene; Risk; Role; Sensory; Sensory Receptors; Smell Perception; Stimulus; Synaptic Transmission; Synaptic plasticity; System; Taste Perception; Testing; Tongue; Work; adolescent alcohol abuse; age group; alcohol exposure; alcohol research; alcohol response; base; behavioral genomics; behavioral response; chorda tympani; clinical development; clinical predictors; clinically relevant; experience; fetal; interdisciplinary approach; lingual nerve; maternal alcohol use; nerve supply; neurodevelopment; neurophysiology; novel; offspring; olfactory bulb; oral irritation; preference; prenatal; prenatal exposure; receptor; receptor expression; relating to nervous system; response; therapy development

Fetal ethanol exposure is highly predictive of ethanol abuse in adolescence, and there is an inverse correlation between the age of first experience and the likelihood of continued abuse. How does fetal exposure alter adolescent ethanol acceptability? How does adolescent re-exposure increase adult acceptance? Are the consequences of fetal and adolescent exposure distinct? The fiavor attributes (smell, taste and oral irritation) of ethanol are important determinants of acceptance. We hypothesize that fetal ethanol exposure induces developmental changes in the neural systems involved in the perception and acceptability of ethanol's flavor, thereby increasing the risk of initial ingestion and continued adolescent abuse. Further, adolescent experience with ethanol augments the fetal effect and/or perpetuates the ethanol-induced changes into adulthood. This proposition is supported by our prior studies and compelling preliminary data demonstrating that fetal ethanol exposure: (1) reduces the peripheral neural taste response to quinine (a surrogate for ethanol's bitter taste) and (2) decreases the expression of bitter (T2r) and oral irritation (Trp) receptor genes fundamental to ethanol flavor perception and intake in adolescent rats. We also find that binge ethanol exposure in naive adolescent rats yields similar results to the prenatal T2r findings. Our long-range goal is to apply an understanding of these cellular processes to the development of clinical treatments and strategies. Applying behavioral, genomic and neurophysiologic methods, the objectives of this proposal are to understand mechanistically: (A) the ontogeny of the fetal exposure effect on oro-sensory receptor gene expression and whether the observed effects differ between fetal and adolescent exposure; (B) whether adolescent behavioral responses (following fetal exposure) are mediated by alterations in receptor gene expression; and (C) whether adolescent re-exposure augments the behavioral and receptor response to fetal exposure and/or perpetuates them into adulthood. We will also determine how alterations in the peripheral neural responses to ethanol and stimuli representing its component qualities (bitter, sweet and irritancy) parallel the foregoing behavioral and genomic effects.

胎儿乙醇暴露高度预测青春期乙醇的滥用，并且首次体验的年龄与持续滥用的可能性之间存在逆相关性。胎儿暴露如何改变青少年乙醇的可接受性？青少年重新曝光如何增加成人的接受度？胎儿和青少年暴露的后果是不同的吗？乙醇的FIAVOR属性（气味，味道和口服刺激）是接受的重要决定因素。我们假设胎儿​​乙醇暴露会引起乙醇风味感知和可接受性的神经系统的发育变化，从而增加了初次摄入的风险和持续的青少年虐待。此外，乙醇的青少年经验增强了胎儿效应和/或使乙醇诱导的成年变化永久化。我们先前的研究和令人信服的初步数据证明了这一主张的支持：（1）降低了对奎宁的外围神经味道的反应（乙醇苦味的替代物（替代乙醇的苦味），（2）降低苦味（T2R）和口服刺激（TRP）受体（TRP）受体基因素质的表达，并浓缩了乙醇的浓度。我们还发现，幼稚青少年大鼠的暴饮暴食乙醇暴露与产前T2R的结果相似。我们的远程目标是将对这些细胞过程的理解应用于临床治疗和策略的发展。采用行为，基因组和神经生理方法，该提案的目标是机械理解：（a）胎儿暴露对Oro-Sensory受体基因表达的影响，以及观察到的胎儿和青少年暴露之间观察到的效果是否有所不同； （b）青少年行为反应（胎儿暴露后）是否通过受体基因表达的改变来介导； （c）青少年重新暴露是否会增加对胎儿暴露的行为和受体反应和/或将其永久化为成年。我们还将确定周围神经对乙醇和刺激的反应的变化如何代表其成分质量（苦，甜和刺激）与上述行为和基因组效应相似。