Effect of chronic ethanol treatment and selective breeding for hypnotic sensitivity to ethanol on intracellular...

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.