Effect of repeated exposure to alcohol on the response of the hypothalamic-pituitary-adrenal axis of the rat: I. Role of changes in hypothalamic neuronal activity
Effect of repeated exposure to alcohol on the response of the hypothalamic-pituitary-adrenal axis of the rat: I. Role of changes in hypothalamic neuronal activity
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DOI：
10.1097/00000374-200101000-00014
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发表时间：
2001-01-01
影响因子：
3.2
通讯作者：
Rivier, C
中科院分区：
文献类型：
--
作者：
Lee, S;Schmidt, ED;Rivier, C
背景：事先（3-12天）注射酒精可显著减弱下丘脑-垂体-肾上腺（HPA）轴对第二次药物刺激的反应，而不会明显改变对其他应激源的反应。因此，我们确定了下丘脑神经元的适应性是否导致了这种活性下降。方法：成年雄性大鼠连续3 d灌胃酒精（4.5 g/kg）或酒精，7 d后再灌胃。测定循环中促肾上腺皮质激素（ACTH）水平、下丘脑室旁核（PVN）中促肾上腺皮质激素释放因子（CRF）、CRF受体1型（CRFR1）和抗利尿激素（VP）转录物水平以及中隆起CRF/VP肽水平。结果：在恢复的第7天，所有动物的CRF、CRFR1和VP的静止PVN水平具有可比性，而在先前暴露于酒精的动物中，中隆起外区CRF和VP的储存量减少。在第7天的急性酒精刺激后，与预先处理的大鼠相比，先前暴露于药物的大鼠的PVN CRF和CRFR1表现出显著（p < 0.01）的抑制，但VP神经元反应没有。结论：PVN CRF神经元活动减弱可能是我们之前报道的在几天前注射酒精的大鼠中ACTH反应下降的原因。此外，尽管PVN VP转录水平相当，但我们观察到，中位隆起中这种肽的较低水平也可能参与了ACTH反应的减弱。
Background: Prior (3-12 days) injection of alcohol significantly blunts the response of the hypothalamic-pituitary-adrenal (HPA) axis to a second drug challenge without measurably altering responses to other stressors. We therefore determined whether adaptation in hypothalamic neurons underlies this decreased activity.Methods: Adult male rats were administered alcohol (4.5 g/kg intragastrically) or vehicle daily for three consecutive days and then were challenged with the vehicle or alcohol 7 days later. Levels of adrenocorticotropin hormone (ACTH) in the circulation, corticotropin-releasing factor (CRF), CRF receptors type 1 (CRFR1) and vasopressin (VP) transcripts in the paraventricular nucleus (PVN) of the hypothalamus, and CRF/VP peptide in the median eminence were measured.Results: Resting PVN levels of CRF, CRFR1, and VP were comparable in all animals on day 7 of recovery, whereas CRF and VP stores in the external zone of the median eminence were decreased in animals previously exposed to alcohol. After the acute alcohol challenge on day 7, rats previously exposed to the drug exhibited a significant (p < 0.01) dampening of their PVN CRF and CRFR1, but not VP neuronal response, compared with vehicle-pretreated rats.Conclusion: Blunted neuronal activity of PVN CRF neurons may be responsible for the decreased ACTH response that we previously reported in rats that had been injected with alcohol several days earlier. In addition, and despite comparable PVN VP transcript levels, the lower levels of this peptide in the median eminence also may participate in the blunted ACTH response that we observed.