Male Wistar rats were examined on the moving belt test at approximately 10, 30 and 60 min after administration of ethanol in doses ranging from 1.0-2.8 g/kg. Immediately after the test, each animal was sacrificed and ethanol concentrations were measured. The regression line of impairment as a function of brain alcohol concentration showed a progressive shift toward higher brain levels with increasing time after alcohol administration. The results confirm the existence of acute tolerance to ethanol, as defined by reduced impairment of function for a given blood level on the falling versus the rising arm of the blood alcohol curve. Confusion of interpretation due to arterio-venous differences in alcohol concentration was ruled out by simultaneous measurements in arterial blood and brain. Practice effects were ruled out by testing each animal only once.

No abstract

The phenomenon of behavioral augmentation of tolerance (BAT) to ethanol (EtOH) in the rat was replicated in studies using the moving belt test of intoxication. Rats performing the test daily under the influence of EtOH (2.2 or 2.5 g/kg i.p.) developed tolerance more rapidly than those receiving the same dose after each daily session on the belt. However, both groups reached the same maximum level of tolerance. Acceleration of tolerance by BAT was proportional to the frequency of performance under the influence of EtOH when total exposure to EtOH was held constant. The degree of tolerance produced by BAT could not be increased by daily gavage with a large dose (6 g/kg) of EtOH. After termination of EtOH administration, tolerance produced by BAT was lost at the same rate, whether or not daily alcohol-free sessions on the belt test were given. These findings are consistent with the hypothesis that BAT and conventionally produced tolerance differ only in rate.

Adult male rats were subjected to 1--4 cycles of daily gastric intubation with ethanol (6 g/kg) for 16 days, separated by 17-day alcohol-free periods. Tolerance produced by this treatment (designated 'physiological tolerance') was measured by change in effect of a 2.2 g/kg i.p. dose of ethanol on the moving-belt test. It occurred in each cycle, disappeared completely in the drug-free periods, and developed more rapidly in the second and later cycles than in the first. Tolerance produced by the 'behavioral augmentation' technique (daily test practice under the influence of ethanol) also developed more rapidly on a second than on a first cycle. The progression from within-session to between-session tolerance was still evident, but accelerated. With 25-day alcohol cycles, separated by a one-month drug-free period, the 'carry-over' effect (i.e., more rapid acquisition of tolerance in the second cycle) applied equally, regardless of whether or not tolerance was produced by the same technique in both cycles, or by a crossover in either direction between the two techniques.

Adult rats, required to perform a motor coordination task while under the influence of ethanol (2.2 g/kg) daily for 12 days, developed significant tolerance to the effects of ethanol, not only on this test but also on a food-motivated maze task. At the same time, they showed reduced shock threshold for production of a startle response, and reduced open field test scores 23 hrs after the last dose of ethanol. Other animals receiving the same dose of ethanol immediately after each training session on the coordination task, and others performing the task and receiving no ethanol, showed no tolerance on either test and no change in shock threshold or open field behavior. The results suggest that behaviorally augmented tolerance depends on basic neuronal adaptive changes indistinguishable from those accompanying physiological tolerance and dependence.