Zgombick J M, Erwin V G
Alcohol Research Center, School of Pharmacy, University of Colorado, Boulder 80309.
Alcohol. 1988 Jul-Aug;5(4):287-94. doi: 10.1016/0741-8329(88)90067-5.
The stimulatory effect of ethanol on the hypothalamo-pituitary-adrenal (HPA) axis was investigated in the long-sleep (LS) and short-sleep (SS) lines of mice. Plasma corticosterone concentrations peaked 30 min after IP administration of ethanol in both lines of mice. Ethanol produced dose-dependent elevations in plasma corticosterone in both LS and SS mice; however, at low doses of ethanol (0.25 to 1 g/kg) the adrenocortical response observed in LS mice was markedly greater than in SS mice. Passive immunoneutralization of circulating corticotropin releasing factor (CRF) completely abolished ethanol-induced elevation in plasma corticosterone in LS mice. CRF or ACTH (adrenocorticotropin) produced dose-dependent elevations in plasma corticosterone in the two lines of mice. Epinephrine co-administered with CRF did not potentiate the adrenocortical response obtained with CRF in either line of mice, and hexamethonium only slightly attenuated ethanol-induced elevations in plasma corticosterone in both lines of mice, suggesting that differentially elevated plasma catecholamines are not responsible for differences in ethanol-induced adrenocortical response. The results suggest that differential adrenocortical response to ethanol exhibited by LS and SS mice is due primarily to differential ethanol-induced CRF release.
在小鼠的长睡眠(LS)和短睡眠(SS)品系中研究了乙醇对下丘脑 - 垂体 - 肾上腺(HPA)轴的刺激作用。腹腔注射乙醇后30分钟,两个品系小鼠的血浆皮质酮浓度均达到峰值。乙醇使LS和SS小鼠的血浆皮质酮呈剂量依赖性升高;然而,在低剂量乙醇(0.25至1 g/kg)时,LS小鼠中观察到的肾上腺皮质反应明显大于SS小鼠。循环促肾上腺皮质激素释放因子(CRF)的被动免疫中和完全消除了LS小鼠中乙醇诱导的血浆皮质酮升高。CRF或促肾上腺皮质激素(ACTH)使两个品系小鼠的血浆皮质酮呈剂量依赖性升高。与CRF共同给药的肾上腺素在两个品系小鼠中均未增强CRF引起的肾上腺皮质反应,六甲铵仅略微减弱了两个品系小鼠中乙醇诱导的血浆皮质酮升高,这表明血浆儿茶酚胺差异升高不是乙醇诱导的肾上腺皮质反应差异的原因。结果表明,LS和SS小鼠对乙醇表现出的不同肾上腺皮质反应主要是由于乙醇诱导的CRF释放差异。