Effects of chronic treatment with ethanol on the development of cross-tolerance to other alcohols and pentobarbital.
The development of cross-tolerance to various alcohols and pentobarbital was examined in ethanol (EtOH)-treated mice. Chronic EtOH treatment (dosage rising in steps from 3.5-4.5 g/kg i.p. daily during a 23-day period) produced tolerance to its hypnotic effect. Such tolerance was seen as a reduction in the duration of loss of righting reflex (LRR), as well as higher blood EtOH levels at the offset of LRR, in EtOH-treated mice as compared to saline-treated controls. Cross-tolerance was shown by shifts in dose-response curves for the LRR induced by n-propanol and t-butanol. Such treatment, however, did not confer functional cross-tolerance to n-butanol and pentobarbital. Because n-butanol and pentobarbital are more lipid-soluble, whereas EtOH, n-propanol and t-butanol have low degrees of lipid solubility, the development of cross-tolerance among these sedative-hypnotic drugs might be related to their relative degrees of lipid solubility.
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Department of Primary Mechanisms Research and Development, Addiction Research Foundation of Ontario, Toronto, Canada.
Khanna
J M
JM
Kalant
H
H
D020001:1-Butanol; D000433:1-Propanol / Q000097:blood / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000440:Butanols / Q000097:blood / Q000494:pharmacology; D004361:Drug Tolerance; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D010424:Pentobarbital / Q000097:blood / Q000494:pharmacology; D012018:Reflex / Q000187:drug effects; D012890:Sleep / Q000187:drug effects
D000440:Butanols; D006993:Hypnotics and Sedatives; D000431:Ethanol; D020001:1-Butanol; D000433:1-Propanol; D010424:Pentobarbital