Arnhold Michelle M, Wotus Cheryl, Engeland William C
Departments of Surgery and Neuroscience, Graduate Program in Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
Exp Neurol. 2007 Jul;206(1):126-36. doi: 10.1016/j.expneurol.2007.04.010. Epub 2007 May 3.
Acute activation of the hypothalamic-pituitary-adrenal (HPA) axis releases glucocorticoids to maintain homeostasis, whereas prolonged exposure to elevated glucocorticoids has deleterious effects. Due to the potential benefits of limiting stress-induced glucocorticoid secretion, the present study uses drinking in dehydrated rats as a model to delineate mechanisms mobilized to rapidly inhibit HPA activity during stress. Using Fos expression as an indicator of neuronal activation, the effect of a single or repeated episode of dehydration-induced drinking on the activity of magnocellular and parvocellular neurons in the paraventricular nucleus (PVN) of the hypothalamus was examined. Adult male rats underwent a single episode or repeated (six) episodes of water restriction and were sacrificed before or after drinking water in the AM. Plasma osmolality, vasopressin (AVP), adrenocorticotropic hormone (ACTH) and corticosterone were elevated by water restriction and reduced after drinking in both models. Fos expression was elevated in AVP-positive magnocellular PVN neurons and AVP- and corticotropin releasing hormone (CRH)-positive parvocellular PVN neurons after water restriction. Fos expression was reduced in magnocellular AVP neurons after both models of restriction-induced drinking. In contrast, Fos expression did not change in AVP and CRH parvocellular neurons after a single episode of restriction-induced drinking, but was reduced after repeated episodes of restriction-induced drinking. These data indicate that drinking-induced decreases in glucocorticoids in dehydrated rats involve multiple factors including reduction in magnocellular release of vasopressin and reduction in parvocellular neuronal activity. The differential inhibition of PVN parvocellular neurons after repeated rehydration may reflect a conditioned response to repeated stress reduction.
下丘脑 - 垂体 - 肾上腺（HPA）轴的急性激活会释放糖皮质激素以维持体内平衡，而长期暴露于升高的糖皮质激素则具有有害影响。由于限制应激诱导的糖皮质激素分泌具有潜在益处，本研究以脱水大鼠的饮水行为作为模型，来阐明在应激期间迅速抑制HPA活性所调动的机制。以Fos表达作为神经元激活的指标，研究了单次或重复的脱水诱导饮水对下丘脑室旁核（PVN）大细胞和小细胞神经元活动的影响。成年雄性大鼠经历单次或重复（六次）限水过程，并在上午饮水前或饮水后处死。在两种模型中，限水都会使血浆渗透压、血管加压素（AVP）、促肾上腺皮质激素（ACTH）和皮质酮升高，而饮水后则降低。限水后，AVP阳性大细胞PVN神经元以及AVP和促肾上腺皮质激素释放激素（CRH）阳性小细胞PVN神经元中的Fos表达升高。在两种限水诱导饮水模型后，大细胞AVP神经元中的Fos表达均降低。相比之下，单次限水诱导饮水后，AVP和CRH小细胞神经元中的Fos表达没有变化，但在重复限水诱导饮水后降低。这些数据表明，脱水大鼠中饮水诱导的糖皮质激素减少涉及多种因素，包括大细胞血管加压素释放减少和小细胞神经元活动减少。重复补液后对PVN小细胞神经元的差异性抑制可能反映了对重复应激减轻的条件反应。
