Neural Plasticity and Sensitization of Salt Appetite

描述(由申请人提供)：盐的摄入量和喜好特别令人感兴趣，因为高盐摄入量与高血压的病因有关。食盐是对钠缺乏的一种行为反应，表现为对高渗氯化钠溶液的狂热消费。食盐的食欲受到敏感化的影响，即钠耗竭的发作会导致随后的食盐耗竭后食盐食欲的增加。此外，在大鼠中，急性钠耗竭会引起神经元形态的改变，伏隔核神经元中的树突和棘突增加。令人惊讶的是，这些神经元的变化与观察到的与某些成瘾药物的敏化有关的变化非常相似。这项拟议的研究将研究先前钠耗竭对钠食欲的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。行为和生理操作将包括给药利钠/利尿剂速尿，以产生钠消耗和促进钠的食欲。伏隔核神经元的形态将用高尔基染色的材料进行分析，包括评估树突的总长度、分支长度和数量以及棘细胞的数量和密度。长期目标是检验这一假说，即盐和药物敏化常见的神经元变化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.