Neural Plasticity and Sensitization of Salt Appetite

神经可塑性和盐食欲的敏感性

• 批准号: 7088888
• 负责人: ILENE L BERNSTEIN
• 金额: $ 18.05万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7088888
• 关键词: Golgi apparatus; aldosterone; angiotensins; antigen antibody reaction; appetite; brain morphology; computer program /software; cytoskeletal proteins; dendrites; drug hypersensitivity; furosemide; gene expression; laboratory rat; neural plasticity; neuropharmacology; nucleus accumbens; regulatory gene; salts; saluretic; sodium chloride

DESCRIPTION (provided by applicant): Salt intake and preference are of particular interest because high salt intake has been implicated in the etiology of hypertension. Salt appetite is a behavioral response to a sodium deficit and is expressed as avid consumption of hypertonic NACl solutions. Salt appetite is subject to sensitization, namely episodes of sodium depletion lead to increased salt appetite following subsequent depletions. Additionally, episodes of acute sodium depletion, in rats, cause an alteration in neuronal morphology with increased dendritic branches and spines in neurons in the nucleus accumbens. Strikingly, these neuronal alterations are remarkably similar to those observed in association with the sensitization to certain addictive drugs. The proposed studies will examine the relationship between sensitization of sodium appetite by prior sodium depletions and altered dendritic morphology in the nucleus accumbens and will assess the relationship of these changes to those associated with drug sensitization. Behavioral and physiological manipulations will involve administration of the natriuretic/diuretic agent, furosemide to produce sodium depletion and promote a sodium appetite. Morphology of neurons in the nucleus accumbens will be analyzed in Golgi stained material and include assessment of total dendritic length, branch length and number as well as spine number and density. The long range goal is to examine the hypothesis that neuronal alterations common to salt and drug sensitization represent a general neuronal response to a strong physiological challenge that provides a mechanism for an enhanced behavioral response to subsequent exposures to that challenge.

描述（由申请人提供）：盐的摄入量和偏好特别令人感兴趣，因为高盐摄入量与高血压的病因有关。盐食欲是对钠缺乏的行为反应，表现为对高渗 NACl 溶液的狂热消耗。盐的食欲会受到敏化的影响，即钠消耗的发作会导致随后的钠消耗增加。此外，大鼠急性缺钠会导致神经元形态发生改变，伏隔核神经元的树突分支和棘增加。引人注目的是，这些神经元改变与观察到的与对某些成瘾药物过敏相关的改变非常相似。拟议的研究将检查先前钠消耗引起的钠食欲敏化与伏核中树突形态的改变之间的关系，并将评估这些变化与药物敏化相关的变化之间的关系。行为和生理操作将涉及施用利尿钠/利尿剂、速尿以产生钠消耗并促进钠食欲。将在高尔基体染色材料中分析伏隔核中神经元的形态，包括评估总树突长度、分支长度和数量以及棘数量和密度。长期目标是检验这样的假设：盐和药物敏化所常见的神经元改变代表了对强烈生理挑战的一般神经元反应，这为随后暴露于该挑战提供了增强行为反应的机制。