Neural Plasticity and Sensitization of Salt Appetite

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，并表示为高渗NaCl溶液的贪婪消耗。盐食欲易受致敏作用的影响，即钠消耗的发作导致随后的消耗后盐食欲增加。此外，在大鼠中，急性钠耗竭的发作引起神经元形态的改变，在丘脑核中的神经元中具有增加的树突分支和棘。令人惊讶的是，这些神经元的改变与某些成瘾药物致敏相关的观察结果非常相似。拟议的研究将检查先前钠缺乏引起的钠食欲敏感化与延髓核中树突形态改变之间的关系，并将评估这些变化与药物致敏相关变化之间的关系。行为和生理操作将涉及钠尿/利尿剂、呋塞米的给药，以产生钠耗竭并促进钠食欲。将在高尔基体染色材料中分析丘脑核中神经元的形态，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，即盐和药物致敏共同的神经元改变代表了对强生理挑战的一般神经元反应，该生理挑战提供了对随后暴露于该挑战的增强的行为反应的机制。

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.