Chronic ethanol exposure results in increased acute functional tolerance in selected lines of HAFT and LAFT mice

Rationale ann objectives: Functional (pharmacodynamic) ethanol tolerance ca n be evidenced within a single session of exposure to ethanol (acute or wit hin-session tolerance), or after repeated ethanol exposures (chronic or bet ween-session tolerance). To investigate whether acute and chronic tolerance to ethanol are inter-related phenomena, the effect of chronic ethanol expo sure was evaluated in mice selectively bred for high (HAFT) or low (LAFT) a cute functional tolerance to an ataxic effect of ethanol, i.e., loss of bal ance on a stationary dowel. Methods: Mice were tested for sensitivity (thre shold ethanol concentration for loss of balance on the stationary dowel) an d acute functional tolerance to ethanol before and after a regimen of chron ic ethanol exposure (twice-daily ethanol injections for 6 days). Results: C hronic ethanol treatment did not alter the threshold for ethanol's ataxic e ffect (i.e., produced no change in sensitivity). However, this treatment, i n a dose-dependent manner, resulted in an increase in the magnitude and rat e of development of acute functional tolerance. Conclusions: This finding s upports previous postulates that chronic ethanol tolerance can be character ized by a more rapid acquisition or a greater magnitude of acute (within-se ssion) tolerance. However, the increase in acute tolerance that occurred af ter chronic ethanol exposure was similar in both selected lines of mice, in dicating little or no genetic correlation between acute tolerance and chron ic tolerance.