Rapid tolerance and cross-tolerance as predictors of chronic tolerance and cross-tolerance.
Hypothermia and motor impairment (tilt-plane) tests were used to assess the phenomenon of rapid tolerance to ethanol and cross-tolerance to various alcohols, benzodiazepines, and barbiturates that differ in lipid:water partition coefficients. The hypothermic and motor impairment responses to ethanol were significantly reduced on day 2 in rats receiving ethanol (2 doses of 2 g/kg each for the hypothermia test and 2.3 and 1.7 g/kg for the tilt-plane test) 24 and 22 h earlier compared to the control group pretreated with saline. Ethanol pretreatment resulted in rapid cross-tolerance, on both tests, to the various alcohols (n-propanol, n-butanol, and t-butanol) and the benzodiazepines (chlordiazepoxide, diazepam, oxazepam, and flurazepam) tested. Ethanol pretreatment also conferred clear rapid cross-tolerance to barbital and phenobarbital, but did not result in rapid cross-tolerance to pentobarbital, secobarbital, amobarbital, or thiopental. The results on rapid cross-tolerance on both tests seen in these studies parallel the results obtained in chronic tolerance and cross-tolerance studies reported recently. These results suggest that rapid tolerance and cross-tolerance can be used as predictors of chronic tolerance and cross-tolerance.
Khanna
J M
JM
Department of Pharmacology, University of Toronto, Canada.
Kalant
H
H
Weiner
J
J
Shah
G
G
D000438:Alcohols / Q000494:pharmacology; D000818:Animals; D001463:Barbiturates / Q000494:pharmacology; D004361:Drug Tolerance / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology; D007035:Hypothermia / Q000139:chemically induced; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000438:Alcohols; D001463:Barbiturates; D000431:Ethanol