Functional Mapping of Ethanol Avoidance in Mouse Pain

描述(由申请人提供)：当比较两个品系的小鼠时观察到反对乙醇的自我给药行为：C57BL/6J x NZB/B1NJ F1杂交种(B6xNZB)在经历了高浓度乙醇后避免乙醇(回避者)和C57BL/6J x FVB/NJ F1杂交种(BGxFVB)不(狂欢者)。这一应用的最重要的假设是，这些杂交细胞对酒精的厌恶性质的敏感性不同，但不是奖励或缓解焦虑的性质，以及特定细胞类型和大脑区域中FosB和DeltaFosB的不同水平反映了自愿服用乙醇的经验依赖的差异。杂交种对乙醇的厌恶、奖励和抗焦虑特性的敏感性将通过以下测试来确定：条件性味觉厌恶、条件性位置偏好、改进的两瓶选择和提升的加迷宫。为了确定酒精避免和狂欢所涉及的神经回路，将在有酒精经验的杂交后代中测量FosB和DeltaFosB的免疫反应性。表达FosB和DeltaFosB的神经元的神经细胞类型也将被确定。FosB/DeltaFosB阳性核(每个脑区和细胞类型)的应变、剂量和数量的影响将被确定。这些实验将有助于理解酒精的使用和滥用。

DESCRIPTION (provided by applicant): Opposing ethanol self-administration behaviors are observed when comparing two strains of mice: C57BL/6J x NZB/B1NJ F1 hybrids (B6xNZB) avoid ethanol (avoiders) after experience with high concentrations of ethanol and C57BL/6J x FVB/NJ F1 hybrids (BGxFVB) do not (revelers). The overarching hypothesis of this application is that these hybrids differ in sensitivity to the aversive, but not rewarding or anxiolytic, properties of ethanol and differential levels of FosB and deltaFosB in specific cell types and brain regions reflects experience dependent differences in voluntary ethanol self-administration. Hybrid sensitivity to aversive, rewarding, and anxiolytic properties of ethanol will be determined by employing the following tests; conditioned taste aversion, conditioned place preference, modified two bottle choice, and elevated plus maze. To define neurocircuits engaged by ethanol avoidance and revelry, FosB and deltaFosB immunoreactivity will be measured in ethanol experienced hybrids. Neuronal cell types of FosB and deltaFosB expressing neurons will also be determined. Effects of strain, dose, and quantity of FosB/deltaFosB positive nuclei (per brain region and cell type) will be determined. These experiments will contribute to the understanding of alcohol use and abuse.