A simple procedure using 4-methylpyrazole for developing tolerance and other chronic alcohol effects.
Young rats given ethanol chronically by gradually increasing the concentration in the drinking fluid to 17.5% reached a maximal daily consumption of 15-17 g ethanol/kg body wt., which corresponded to 35-40% of their energy intake. This chronic treatment was markedly potentiated by additional supplementation of the drinking fluid with a low dose of the alcohol dehydrogenase inhibitor 4-methylpyrazole. Rats on this regimen exhibited higher and more sustained blood ethanol levels. Consequently, more pronounced functional and metabolic tolerance developed and more frequent signs of physical dependence was observed than in rats drinking only ethanol solution. Simple provision of drinking fluid supplemented with ethanol and 4-methylpyrazole appears to provide a nutritionally adequate and easy way to produce tolerance and other chronic alcohol effects.
D000818:Animals; D004357:Drug Synergism; D004361:Drug Tolerance; D000431:Ethanol / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D000077604:Fomepizole; D006801:Humans; D008297:Male; D011720:Pyrazoles / Q000008:administration & dosage* / Q000097:blood; D051381:Rats; D013375:Substance Withdrawal Syndrome
D011720:Pyrazoles; D000431:Ethanol; D000077604:Fomepizole