Rapid ethanol tolerance mediated by adaptations in acute tolerance in inbred mouse strains

It has been postulated that decreased acute sensitivity to ethanol is an important genetically-mediated risk factor for the development of alcoholism. Previous work in mice and rats has indicated that ethanol sensitivity can be reduced in a genotype-dependent manner by a single dose of ethanol 24 h prior to testing, so-called 'rapid' tolerance. The current studies were undertaken to determine if the observed rapid tolerance was mediated by alterations in initial sensitivity or acute functional tolerance (AFT), the two primary components of acute sensitivity. Separate groups of C57BL/6, DBA/2, ILS, and ISS inbred mouse strains were administered a single pretreatment dose of saline or ethanol (5 g/kg). The original and modified versions of the loss of righting reflex test, ethanol-induced hypothermia, and ataxia on a stationary dowel rod were tested 24 h later. Dependent on the test and strain, varying degrees of rapid tolerance were observed; a pronounced sensitization was detected in one case. There was a concomitant increase in the rate and/or magnitude of AFT with little change in initial sensitivity suggesting that rapid tolerance was mediated primarily by alterations in AFT. This conclusion may have implications for the contribution of acute sensitivity to human alcoholism.