Effect of two iron-chelators, desferrioxamine and diethylenetriaminepentaacetic acid, on the development of tolerance to the physical dependence on ethanol in mice.
Physical dependence on ethanol was induced in mice by exposing the animals to increasing concentrations of ethanol vapor for a period of 9 days. The degree of dependence was assessed by subjective scoring of a characteristic behavioral withdrawal syndrome upon cessation of ethanol administration. The daily administration of desferrioxamine (350 mg/kg, i.p.) or of diethylenetriaminepentaacetic acid (200 mg/kg, i.p.) during the ethanol treatment period reduced by 50% the behavioral withdrawal score. On the other hand, an iron-load of 250 mg/kg administered once prior to ethanol treatment and once during ethanol exposure caused a significant increase in the withdrawal score. While the degree of dependence was significantly lowered by the iron chelators, the state of tolerance after chronic ethanol treatment was not altered by these agents. However, the capacity of these ethanol-treated animals to develop rapid functional tolerance at termination of the chronic ethanol exposure was significantly enhanced by desferrioxamine and diethylenetriaminepentaacetic acid. The results are discussed in view of possible role of iron-induced peroxidation of neuronal membrane lipids in the development of tolerance to and dependence on, ethanol.
D000818:Animals; D003676:Deferoxamine / Q000627:therapeutic use*; D004361:Drug Tolerance; D000431:Ethanol; D006801:Humans; D008297:Male; D051379:Mice; D004369:Pentetic Acid / Q000627:therapeutic use*; D019966:Substance-Related Disorders / Q000517:prevention & control*
D000431:Ethanol; D004369:Pentetic Acid; D003676:Deferoxamine