Hellriegel E T, D'Mello A P
Department of Pharmaceutics, Philadelphia College of Pharmacy and Science, PA 19104, USA.
Pharmacol Biochem Behav. 1997 May-Jun;57(1-2):207-14. doi: 10.1016/s0091-3057(96)00341-3.
The objective of this investigation was to examine the immediate and long term effects of acute, chronic and chronic intermittent stress on the central noradrenergic system of rats. Male Sprague-Dawley rats were subjected to one hour of physical immobilization stress either as a single exposure, or as 14 exposures applied either on consecutive days, or randomly over 60 days. Animals were sacrificed immediately, 6 h and 24 h following the last stressor. Levels of norepinephrine (NE) and 3-methoxy-4-hydroxyphenylethylene-glycol sulfate (MHPG-sulfate) were measured in the hypothalamus, hippocampus, cerebral cortex and locus coeruleus region and beta-adrenergic receptor (BAR) density was determined in the cortex. Immediately after acute stress, a significant reduction in hypothalamic NE levels and marked increases in MHPG-sulfate levels in all four brain regions were observed. In contrast immediately after the last stressor of a chronic or chronic intermittent stress regimen, no change in NE concentration was observed while levels of MHPG-sulfate in the four brain regions showed a smaller increase than that observed after an acute stressor. Acute stress induced changes normalized within 6 h while chronic and chronic intermittently stressed animals had altered NE or MHPG-sulfate levels in certain brain regions for up to 6-24 h. Cortical BAR binding parameters remained unchanged after all stress paradigms.
本研究的目的是检测急性、慢性和慢性间歇性应激对大鼠中枢去甲肾上腺素能系统的即时和长期影响。将雄性斯普拉格-道利大鼠进行1小时的身体束缚应激,应激方式为单次暴露,或连续14天暴露,或在60天内随机暴露。在最后一次应激后立即、6小时和24小时处死动物。测定下丘脑、海马、大脑皮层和蓝斑区域中去甲肾上腺素(NE)和3-甲氧基-4-羟基苯乙二醇硫酸盐(MHPG-硫酸盐)的水平,并测定皮层中的β-肾上腺素能受体(BAR)密度。急性应激后立即观察到,所有四个脑区的下丘脑NE水平显著降低,而MHPG-硫酸盐水平显著升高。相比之下,在慢性或慢性间歇性应激方案的最后一次应激后立即观察到,NE浓度没有变化,而四个脑区的MHPG-硫酸盐水平的升高幅度小于急性应激后观察到的升高幅度。急性应激诱导的变化在6小时内恢复正常,而慢性和慢性间歇性应激的动物在某些脑区的NE或MHPG-硫酸盐水平在长达6 - 24小时内发生改变。在所有应激模式后,皮层BAR结合参数均保持不变。