PKA and NPY Signaling in Ethanol-Induced Sensitization

乙醇诱导致敏中的 PKA 和 NPY 信号转导

• 批准号: 7317358
• 负责人: Dayna M. Hayes
• 金额: $ 2.97万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7317358
• 关键词: Address; Alcohol consumption; Alcohols; Amygdaloid structure; Brain region; Breeding; Characteristics; Code; Corpus striatum structure; Cyclic AMP-Dependent Protein Kinases; Elderly; Ethanol; Fees; Immunohistochemistry; Literature; Messenger RNA; Motor Activity; Mus; Mutant Strains Mice; Neurobiology; Nucleus Accumbens; Polymerase Chain Reaction; Protein Overexpression; Rattus; Recombinants; Relative (related person); Signal Transduction; Site; Techniques; Testing; Time; Ventricular; Viral Vector; Y protein; adeno-associated viral vector; alcohol effect; alcohol response; alcohol sensitivity; behavioral sensitization; insight; neuropeptide Y; promoter; vector

Low neuropeptide Y (NPY) and cAMP-dependent protein kinase A (PKA) signaling are both associated with increased ethanol consumption and enhanced sensitivity to ethanol-induced locomotor stimulation. Recent evidence shows that PKA signaling drives NPY synthesis. Therefore, the guiding hypothesis of the present proposal is that the increased ethanol intake and sensitivity to ethanol-induced locomotor sensitization that are characteristic of mutant mice with low central PKA activity (i.e., Rll-beta deficient mice) are consequences of blunted NPY signaling. Specific Aim 1 will utilize immunohistochemistry and real-time PCR to determine if PKA mutant mice have low NPY signaling at baseline and in response to ethanol administration in candidate brain regions. Specific Aim 2 will utilize a recombinant adeno-associated viral vector (rAAV) to determine if site-directed overexpressioh of NPY in the striatum, nucleus accumbens, and/or amygdala will protect against increased sensitivity to ethanol-induced locomotor sensitization and elevated ethanol drinking in PKA mutant mice. These studies will provide important insight into the interactions between PKA and NPY signaling in modulating neurobiological responses to ethanol.

低神经肽Y（NPY）和cAMP依赖性蛋白激酶A（PKA）信号都与 增加乙醇消耗并增强对乙醇诱导的运动刺激的敏感性。最近的 有证据表明，PKA信号传导驱动NPY合成。因此，当前的指导假设 提议是，乙醇摄入量增加和对乙醇引起的运动敏化的敏感性， 是中央PKA活性低的突变小鼠的特征（即RLL-β缺乏小鼠）是 NPY信号传导的后果。特定目标1将利用免疫组织化学和实时PCR 确定PKA突变小鼠在基线时是否具有低NPY信号传导和对乙醇的响应 候选大脑区域的管理。特定目标2将利用重组腺相关病毒 矢量（RAAV）确定纹状体中NPY的位置定向的过表达，伏隔核， 和/或杏仁核将防止对乙醇诱导的运动敏化和 PKA突变小鼠的乙醇饮用升高。这些研究将为您提供重要的见解 PKA与NPY信号之间的相互作用在调节对乙醇的神经生物学反应中。