Szabó G, Kovács G L, Székeli S, Telegdy G
Alcohol. 1985 Jul-Aug;2(4):567-74. doi: 10.1016/0741-8329(85)90082-5.
Mice were made tolerant to the hypothermic effect of ethanol by repeated administration of ethanol (4 g/kg, 25% v/v, IP) on three consecutive days. The colonic temperature was measured in individually-housed animals immediately before and 45 min after ethanol treatment. Peptide treatments with various schedules were made SC 2 hr before the first ethanol challenge. The decrease in hypothermic response was accepted as a tolerance phenomenon, which developed in control animals by day 2. A single injection of oxytocin (OXT) or lysine vasopressin (LVP [0.1 or 1 IU peptide] animal) before the first ethanol injection did not change the initial sensitivity to ethanol. This absence of acute interactions is also reflected in the sleep onset and sleep duration after 5 g/kg ethanol (IP). In contrast, both OXT and LVP affected the development of tolerance. Repeated treatments with graded doses of OXT (0.5-2 IU) or LVP (0.25-1 IU) every day for 3 days blocked the development of tolerance. 0.002 IU LVP facilitated the development of hypothermic tolerance. The remaining doses of the peptides were ineffective. A high dose of LVP (1 IU) facilitated hypothermic tolerance if the peptide was injected when tolerance to ethanol had developed fully without previous peptide treatment. OXT, on the other hand, was ineffective in this particular experimental model. The data suggest that both neurohypophyseal hormones (LVP and OXT) block the early developmental phase of tolerance to ethanol. On the other hand, LVP facilitated the expression of tolerance if the peptide was given to mice with fully developed tolerance.
通过连续三天重复腹腔注射乙醇（4克/千克，25%体积/体积），使小鼠对乙醇的体温过低效应产生耐受性。在乙醇处理前及处理后45分钟，对单独饲养的动物测量结肠温度。在首次乙醇激发前2小时进行皮下注射各种给药方案的肽类。低温反应的降低被视为一种耐受现象，对照动物在第2天出现这种现象。在首次注射乙醇前单次注射催产素（OXT）或赖氨酸加压素（LVP[0.1或1国际单位肽/只动物]）不会改变对乙醇的初始敏感性。这种缺乏急性相互作用的情况也反映在腹腔注射5克/千克乙醇后的入睡时间和睡眠时间上。相比之下，OXT和LVP都影响耐受性的发展。连续3天每天用分级剂量的OXT（0.5 - 2国际单位）或LVP（0.25 - 1国际单位）重复处理可阻断耐受性的发展。0.002国际单位的LVP促进低温耐受性的发展。其余剂量的肽类无效。如果在未预先进行肽类处理且对乙醇的耐受性已完全发展时注射高剂量的LVP（1国际单位），则可促进低温耐受性。另一方面，在这个特定的实验模型中，OXT无效。数据表明，两种神经垂体激素（LVP和OXT）都阻断了对乙醇耐受性的早期发展阶段。另一方面，如果将肽类给予耐受性已完全发展的小鼠，LVP可促进耐受性的表达。
