Synaptic Correlates of Ethanol-Related Behaviors

乙醇相关行为的突触关联

• 批准号: 7470154
• 负责人: JEFFREY L WEINER
• 金额: $ 17.46万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-15 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7470154
• 关键词: Acoustics; Acute; Address; Age; Alcohol consumption; Animals; Anti-Anxiety Agents; Anxiety; Behavior; Behavioral; Boxing; Brain; Brain region; Cells; Chromosome Pairing; Consummatory Behavior; Consumption; Daily; Data; Dependence; Development; Elements; Ethanol; Experimental Designs; Goals; Hippocampus (Brain); Intake; Intoxication; Long-Evans Rats; Matched Group; Measurable; Measures; Mediating; Methods; Modeling; Numbers; Pattern; Physiological; Pilot Projects; Procedures; Property; Rattus; Recording of previous events; Relative (related person); Role; Self Administration; Self-Administered; Slice; Standards of Weights and Measures; Sucrose; Synapses; Synaptic Transmission; System; Testing; Training; Treatment Protocols; Work; age group; alcohol behavior; alcohol effect; alcohol exposure; alcohol sensitivity; base; cohort; design; drinking; drinking behavior; experience; patch clamp; receptor; trait

DESCRIPTION (provided by applicant): Numerous studies have shown that acute ethanol exposure significantly potentiates GABAA receptor-mediated synaptic transmission in the hippocampus and many other brain regions. These, and other, important findings have led to the popular hypothesis that ethanol's acute facilitatory effects on GABAergic synapses contribute to ethanol drinking, intoxication, and dependence. Although this hypothesis has received considerable indirect support, relatively few studies have demonstrated a relationship between ethanol enhancement of GABAergic synapses and any ethanol-related behaviors. In this pilot project, we seek to build on some recent advances in our understanding of the mechanisms through which ethanol enhances GABAergic synapses in the hippocampus, and the role of the hippocampal GABAergic system in ethanol drinking, to examine the relationship between ethanol drinking-related behaviors and the ethanol sensitivity of hippocampal GABAergic synapses. Rats will be trained to self-administer ethanol or sucrose using a well established limited-access paradigm that permits the discrete assessment of "seeking" and "consummatory" drinking behaviors. Aim 1 will test the hypothesis that this voluntary drinking paradigm engenders sufficient ethanol intake to produce measurable reductions in anxiety-like behaviors in standard Long-Evans rats. In Aim 2, brain slices prepared from ethanol- and sucrose-drinking rats, as well as experience-na¿ve controls, will be used in whole-cell patchclamp studies to examine the effects of ethanol self-administration on specific physiological and pharmacological properties of hippocampal GABAergic synapses. Based on preliminary findings, we hypothesize that ethanol self-administration will not alter that acute potentiating effect of ethanol on hippocampal GABAA IPSCs, although possible effects of the self-administration regimen on the properties of GABAergic synapses will be carefully examined. Rather, we hypothesize that the ethanol sensitivity of hippocampal GABAergic synapses may be a trait that is positively correlated with appetitive (or seeking), but not consummatory, ethanol drinking-related behaviors.

描述（由申请人提供）：大量研究表明，急性乙醇暴露显着增强海马体和许多其他大脑区域中 GABAA 受体介导的突触传递。这些以及其他重要发现导致了普遍的假设，即乙醇具有急性促进作用。尽管这一假设得到了相当多的间接支持，但相对较少的研究证明了乙醇增强与酒精依赖之间的关系。 GABA 能突触和任何与乙醇相关的行为在这个试点项目中，我们试图在了解乙醇增强海马 GABA 能突触的机制以及海马 GABA 能系统在乙醇饮用中的作用方面取得一些最新进展。为了检查乙醇饮用相关行为与海马 GABA 突触的乙醇敏感性之间的关系，将训练大鼠自行施用乙醇或。目标 1 将测试这样的假设：这种自愿饮酒模式会产生足够的乙醇摄入量，从而可显着减少焦虑样行为。在目标 2 中，从饮用乙醇和蔗糖的大鼠以及经验中制备的标准 Long-Evans 大鼠的脑切片。 ve 对照，将用于全细胞膜片钳研究，以检查乙醇自我施用对海马 GABA 能突触的特定生理和药理学特性的影响。根据初步发现，我们认为乙醇自我施用不会改变急性增强作用。尽管将仔细检查自我给药方案对 GABA 能突触特性的可能影响，但乙醇对海马 GABAA IPSC 的影响。我们认为海马 GABA 能突触的乙醇敏感性可能是一种与食欲（或寻求）正相关的特征，但与乙醇饮用相关行为无关。