Neural Plasticity and Sensitization of Salt Appetite

描述（由申请人提供）：盐摄入量和偏好是特别感兴趣的，因为高盐摄入与高血压的病因有关。盐的食欲是对钠缺乏的一种行为反应，表现为对高渗盐溶液的强烈消耗。盐的食欲受致敏影响，即钠的消耗会导致盐的食欲增加。此外，大鼠急性钠耗竭发作可引起伏隔核神经元树突状分支和棘增加的神经元形态学改变。引人注目的是，这些神经元的改变与观察到的与某些成瘾药物致敏相关的神经元的改变非常相似。拟议的研究将检查先前钠消耗引起的钠食欲敏化与伏隔核树突形态改变之间的关系，并将评估这些变化与药物敏化相关的关系。行为上和生理上的操作包括使用利钠剂/利尿剂、速尿来产生钠消耗和促进钠的食欲。在高尔基染色材料中分析伏隔核神经元的形态，包括评估总树突长度、分支长度和数量以及棘数和密度。长期目标是检验这样一种假设，即盐和药物致敏引起的神经元改变代表了神经元对强烈生理挑战的一般反应，这种反应为随后暴露于该挑战的增强行为反应提供了一种机制。

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.