P H Wu1, B Tabakoff, G Szabó, P L Hoffman. 1. Department of Pharmacology, University of Colorado Health Sciences Center, 4200E 9th Ave, Box C236, Denver, CO 80262, USA.
Abstract
RATIONALE AND OBJECTIVES: Functional (pharmacodynamic) ethanol tolerance can be evidenced within a single session of exposure to ethanol (acute or within-session tolerance), or after repeated ethanol exposures (chronic or between-session tolerance). To investigate whether acute and chronic tolerance to ethanol are inter-related phenomena, the effect of chronic ethanol exposure was evaluated in mice selectively bred for high (HAFT) or low (LAFT) acute functional tolerance to an ataxic effect of ethanol, i.e., loss of balance on a stationary dowel. METHODS: Mice were tested for sensitivity (threshold ethanol concentration for loss of balance on the stationary dowel) and acute functional tolerance to ethanol before and after a regimen of chronic ethanol exposure (twice-daily ethanol injections for 6 days). RESULTS: Chronic ethanol treatment did not alter the threshold for ethanol's ataxic effect (i.e., produced no change in sensitivity). However, this treatment, in a dose-dependent manner, resulted in an increase in the magnitude and rate of development of acute functional tolerance. CONCLUSIONS: This finding supports previous postulates that chronic ethanol tolerance can be characterized by a more rapid acquisition or a greater magnitude of acute (within-session) tolerance. However, the increase in acute tolerance that occurred after chronic ethanol exposure was similar in both selected lines of mice, indicating little or no genetic correlation between acute tolerance and chronic tolerance.
RATIONALE AND OBJECTIVES: Functional (pharmacodynamic) ethanol tolerance can be evidenced within a single session of exposure to ethanol (acute or within-session tolerance), or after repeated ethanol exposures (chronic or between-session tolerance). To investigate whether acute and chronic tolerance to ethanol are inter-related phenomena, the effect of chronic ethanol exposure was evaluated in mice selectively bred for high (HAFT) or low (LAFT) acute functional tolerance to an ataxic effect of ethanol, i.e., loss of balance on a stationary dowel. METHODS:Mice were tested for sensitivity (threshold ethanol concentration for loss of balance on the stationary dowel) and acute functional tolerance to ethanol before and after a regimen of chronic ethanol exposure (twice-daily ethanol injections for 6 days). RESULTS: Chronic ethanol treatment did not alter the threshold for ethanol's ataxic effect (i.e., produced no change in sensitivity). However, this treatment, in a dose-dependent manner, resulted in an increase in the magnitude and rate of development of acute functional tolerance. CONCLUSIONS: This finding supports previous postulates that chronic ethanol tolerance can be characterized by a more rapid acquisition or a greater magnitude of acute (within-session) tolerance. However, the increase in acute tolerance that occurred after chronic ethanol exposure was similar in both selected lines of mice, indicating little or no genetic correlation between acute tolerance and chronic tolerance.