Daniell L C, Harris R A
Department of Pharmacology, VA Medical Center, Denver, Colorado.
Alcohol Clin Exp Res. 1988 Feb;12(1):179-83. doi: 10.1111/j.1530-0277.1988.tb00156.x.
The effect of chronic ethanol treatment and of selective breeding for hypnotic sensitivity to ethanol on intracellular ionized calcium concentrations (Cai) were examined in mouse whole brain synaptosomes. Following treatment with a liquid diet for 7 days, resting Cai and KCl-stimulated increases in Cai were measured in synaptosomes isolated from chronic ethanol-treated and pair-fed animals. Ethanol (350-700 mM) increased resting Cai and reduced KCl-stimulated increases in Cai in synaptosomes isolated from pair-fed animals. Ethanol-induced changes in Cai were reduced in synaptosomes isolated from chronic ethanol-treated animals. The effect of ethanol on synaptosomal Cai in long-sleep (LS) and short-sleep (SS) mice, selectively bred for differential sensitivity to the hypnotic actions of acute ethanol, was also investigated. In the absence of ethanol, resting values of Cai and KCl-stimulated increases in Cai did not differ between the two lines of mice. Ethanol (200-600 mM) increased resting Cai and reduced depolarization-stimulated increases in Cai in both long-sleep and short-sleep mice to the same degree. Similarly, KCl-stimulated increases in Ca uptake did not differ in synaptosomes isolated from whole brains and cortices of LS and SS mice, in the absence of presence of ethanol. These findings demonstrate that tolerance develops to the effect of ethanol on neuronal Cai following chronic treatment. However, sensitivity to the hypnotic action of ethanol is not related to changes in neuronal Cai in LS and SS mice.
在小鼠全脑突触体中研究了慢性乙醇处理以及对乙醇催眠敏感性进行选择性育种对细胞内游离钙浓度（Cai）的影响。用液体饲料处理7天后，测量从慢性乙醇处理和配对喂养动物分离出的突触体中的静息Cai以及KCl刺激引起的Cai增加。乙醇（350 - 700 mM）使配对喂养动物分离出的突触体中的静息Cai增加，并降低KCl刺激引起的Cai增加。从慢性乙醇处理动物分离出的突触体中，乙醇诱导的Cai变化减少。还研究了乙醇对长期睡眠（LS）和短期睡眠（SS）小鼠突触体Cai的影响，这两种小鼠是为对急性乙醇催眠作用的不同敏感性而选择性培育的。在没有乙醇的情况下，两种品系小鼠的Cai静息值以及KCl刺激引起的Cai增加没有差异。乙醇（200 - 600 mM）使长期睡眠和短期睡眠小鼠的静息Cai增加，并同等程度地降低去极化刺激引起的Cai增加。同样，在有无乙醇的情况下，从LS和SS小鼠全脑和皮质分离出的突触体中，KCl刺激引起的钙摄取增加没有差异。这些发现表明，慢性处理后对乙醇对神经元Cai的作用会产生耐受性。然而，对乙醇催眠作用的敏感性与LS和SS小鼠神经元Cai的变化无关。
