ETHANOL SENSITIZATION, REWARD, AND AVERSION

乙醇敏感、奖励和厌恶

• 批准号: 2707834
• 负责人: CHRISTINA N LESSOV-SCHLAGGAR
• 金额: $ 2.27万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-10 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2707834
• 关键词: alcoholism /alcohol abuse; animal genetic material tag; avoidance behavior; behavioral /social science research tag; behavioral genetics; behavioral habituation /sensitization; ethanol; ethology; laboratory mouse; pharmacogenetics; psychopharmacology; quantitative trait loci; reinforcer; taste

Repeated administration of low ethanol (EtOH) doses may lead to a progressive increase in the motor stimulant effects of EtOH, or behavioral sensitization. The lasting nature of EtOH sensitization points to neural alterations in sensitivity which may effectively maintain EtOH taking behavior leading to EtOH abuse. This proposal aims at investigating the nature of the neural adaptations through molecular and behavioral genetic approaches. First, four quantitative trait loci (QTLs) for EtOH sensitization, identified in a panel of BXDRI strains, will be verified in an F2 intercross of C57BL/6J(B6) and DBA/2J(D2) inbred strains. Four hundred F2 mice will be phenotyped for EtOH sensitization. The most and least sensitized 46 mice will be genotyped for B6 or D2 alleles at each of the four QTLs. Significant associations between the genotype and the phenotype will be statistically identified. Second, the influence of EtOH sensitization on sensitivity to EtOH reinforcement as measured by EtOH two-bottle preference will be examined in 3 mouse genotypes. A difference in EtOH consumption between sensitized mice and nonsensitized controls would imply an effect of EtOH sensitization on EtOH reinforcement efficacy. Third, the influence of EtOH sensitization on sensitivity to EtOH aversion will be examined in a genetically heterogeneous population of mice. EtOH aversion will be assessed using the conditioned taste aversion paradigm. Paring the presentation of 0.2M NaCl flavored solution with one of 3 EtOH or 3 LiCl doses will condition an aversion to the taste of the previously palatable NaC1 solution. Aversion will be evident as a decrease in NaC1 consumption over conditioning trials. This measure will be compared between sensitized and nonsensitized groups. These studies will set the groundwork for future investigation into the utility of EtOH sensitization as an important phenotype in EtOH abuse.

重复施用低剂量的乙醇 (EtOH) 可能会导致 乙醇的运动兴奋作用逐渐增强，或 行为敏化。 乙醇致敏的持久性 指出敏感性的神经改变可能有效 维持导致乙醇滥用的乙醇服用行为。 该提案旨在 通过分子研究神经适应的本质 和行为遗传学方法。 一、四个数量性状位点 在一组 BXDRI 菌株中鉴定出 EtOH 致敏性 (QTL)， 将在 C57BL/6J(B6) 和 DBA/2J(D2) 的 F2 杂交中进行验证 近交系。 将对 400 只 F2 小鼠进行 EtOH 表型分析 敏化。 对最敏感和最不敏感的 46 只小鼠进行基因分型 四个 QTL 中每个 QTL 的 B6 或 D2 等位基因。重要的关联 基因型和表型之间的差异将被统计鉴定。 二、EtOH致敏对EtOH敏感性的影响 将检查通过乙醇两瓶偏好测量的增强效果 3种小鼠基因型。乙醇消耗量的差异 致敏小鼠和非致敏对照意味着乙醇的作用 对乙醇强化功效的敏感性。 三、影响 乙醇敏感性对乙醇厌恶的敏感性将在 具有遗传异质性的小鼠群体。 乙醇厌恶感将会 使用条件味觉厌恶范式进行评估。 削减 使用 3 EtOH 或 3 LiCl 之一呈现 0.2M NaCl 风味溶液 剂量会调节对先前味道的厌恶 适口的 NaC1 溶液。随着 NaC1 的减少，厌恶感将变得明显 消耗超过调节试验。 该措施将被比较 敏感组和非敏感组之间。 这些研究将设定 为未来研究乙醇的效用奠定基础 致敏是乙醇滥用的一个重要表型。