Are changes in neuronal calcium channels involved in ethanol tolerance?
Effects on the development of tolerance to ethanol of concurrent administration of the dihydropyridine calcium channel antagonist, nitrendipine, were investigated. Ethanol tolerance was induced in rats by repeated i.p. injections and measured by performance on the rotarod apparatus. Concurrent injections of nitrendipine prevented the development of tolerance to the ataxic action of ethanol. A similar effect was seen with the calcium channel antagonist PN 200-110 on tolerance to the general anesthetic effects of ethanol in mice. As previously reported, chronic ethanol administration increased the number of dihydropyridine binding sites in rat cerebral cortex. This was also prevented by the nitrendipine treatment; repeated administration of both ethanol and nitrendipine caused a decrease in the number of binding sites. The effect of nitrendipine on the tolerance was not due to alterations in body temperature, changes in blood pressure, differences in brain ethanol concentrations or residual nitrendipine in the brain at the time of testing. The results suggest that alterations in dihydropyridine-sensitive calcium channels may be involved in the adaptations that occur on chronic treatment with ethanol.
Dolin
S J
SJ
Division of Anaesthesia, Clinical Research Centre, Harrow, Middlesex, Great Britain.
Little
H J
HJ
D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D000431:Ethanol / Q000008:administration & dosage* / Q000378:metabolism; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D009553:Nimodipine / Q000378:metabolism; D009568:Nitrendipine / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats
D015220:Calcium Channels; D006584:Hexamethonium Compounds; D018738:Hexamethonium; D000431:Ethanol; D009553:Nimodipine; D009568:Nitrendipine