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Rapid tolerance and cross-tolerance as predictors of chronic tolerance and cross-tolerance

Rapid tolerance and cross-tolerance as predictors of chronic tolerance and cross-tolerance

  1. Bajeda
    Khanna JM, Kalant H, Weiner J, & Shah G. (1992). Rapid tolerance and cross-tolerance as predictors of chronic tolerance and cross-tolerance. Pharmacology Biochemistry and Behaviour, 41(2):355-60.

    Hypothermia and motor impairment (tilt-plane) tests were used to assess the phenomenona 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.