Persistence of tolerance to a single dose of ethanol in the selectively-bred alcohol-preferring P rat

Abstract

The persistence of tolerance to a single dose of ethanol was examined in the selectively-bred alcohol-preferring P line of rats. Tolerance was measured by a test that required trained rats to jump onto a descending platform to avoid footshock. On day 0, each trained rat received a single IP injection of 2.5 g ethanol/kg body weight and was tested every 15 minutes for recovery to a criterion of 75% of pre-alcohol training performance. The second ethanol injection of 2.5 g/kg and testing were carried out seven days later for one group (n = 12), and 14 days later for another group (n = 12). Tolerance was assessed by the differences in time required to recover to criterion performance and blood alcohol concentrations (BACs) at time of recovery on day 0 vs. day 7 and day 14. The mean recovery times and BACs on day 0 were 156±5 minutes and 222±6 mg%, respectively. The group injected on day 7 exhibited shorter recovery times of 113±4 minutes and higher BACs at recovery of 261±4 mg%, while the group injected on day 14 did not show any significant differences from the values obtained on day 0. In a second experiment, the persistence of tolerance in P rats was compared with that of rats from the alcohol-nonpreferring NP line and of stock Wistar rats (n = 6/group). All rats were trained and tested for recovery to criterion after 2.5 g ethanol/kg on day 0 as described for the first experiment. The rats were then injected with ethanol and tested for tolerance on three subsequent occasions. For the P rats, injections were administered after ethanol-free periods of 7, 10 and 14 days, while 3, 7 and 14 day intervals were used for the NP and Wistar rats. The P rats still exhibited tolerance 7 and 10 days (but not at 14 days) following the first dose of ethanol. The NP and Wistar rats, by contrast, showed no significant differences in either recovery times or BACs at time of recovery when injected and tested 3, 7 or 14 days apart. The findings demonstrate that the persistence of acute behavioral (neuronal) tolerance after even a single ethanol exposure is under genetic control and suggest a positive association of this persistence with alcohol drinking preference.