Effect of Chronic Ethanol Treatment and Selective Breeding for Hypnotic Sensitivity to Ethanol on Intracellular Ionized Calcium Concentrations in Synaptosomes

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Abstract
The effect of chronic ethanol treatment and of selective breeding for hypnotic sensitivity to ethanol on intracellular ionized calcium concentrations (Ca1) were examined in mouse whole brain synaptosomes. Following treatment with a liquid diet for 7 days, resting Ca1 and KCl-stimulated increases in Ca1 were measured in synaptosomes isolated from chronic ethanol-treated and pair-fed animals. Ethanol (350–700 mm) increased resting Ca1 and reduced KCl-stimulated increases in Ca1 in synaptosomes isolated from pair-fed animals. Ethanol-induced changes in Ca1 were reduced in synaptosomes isolated from chronic ethanol-treated animals. The effect of ethanol on synaptosomal Ca1 in long-sleap (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 Ca1 and KCl-stimulated increases in Ca1 did not differ between the two lines of mice. Ethanol (200–000 mm) increased resting Ca1 and reduced depolarization-stimulated increases in Ca1 in both long-sleep and short-sleep mice to the same degree. Similarly, KCl-stimulated increases in Ca uptake did not differ in synaptotomes isolated from whole brains and cortices of LS and SS mice, in the absence or presence of ethanol. These findings demonstrate that tolerance develops to the effect of ethanol on neuronal Ca1 following chronic treatment. However, sensitivity to the hypnotic action of ethanol is not related to changes in neuronal Ca1 in LS and SS mice.