Different sensitivity to ethanol in alcohol-preferring sP and -nonpreferring sNP rats

Background and Objectives: Clinical research has proposed that initial sens itivity to ethanol may be negatively correlated with levels of subsequent e thanol intake; consistently, alcohol-preferring P rats were found to be les s sensitive to the ataxic and sedative/hypnotic effects of ethanol than -no npreferring NP rats. The present study investigated the initial sensitivity to the ataxic and sedative/hypnotic effects of ethanol and to the sedative /hypnotic effects of pentobarbital and diazepam in selectively bred Sardini an alcohol-preferring sP and -nonpreferring sNP rats. Methods: In experiment 1, time to lose (onset) and regain (sleep time) the righting reflex after the acute intraperitoneal (ip) administration of 3.0 and 3.5 g/kg ethanol were measured in sP and sNP rats. In experiment 2, sP and sNP rats were required to perform a motor coordination task on a Rota-R od after the acute intragastric administration of 2.0, 2.5, and 3.0 g/kg et hanol. Experiment 3 assessed onset and sleep time in sP and sNP rats after the acute injection of pentobarbital (40 mgikg; ip) and diazepam (15 and 20 mgikg; ip). Results: In experiment I, sP rats took shorter times to lose the righting r eflex and regained this reflex over longer periods of time and at lower blo od ethanol levels than sNP rats. In experiment 2, ethanol affected motor co ordination to a greater extent in sP than sNP rats. In contrast, results fr om experiment 3 showed that sP and sNP rats were not differentially sensiti ve to the sedative/hypnotic effects of pentobarbital and diazepam. Conclusions: The results of experiments 1 and 2 suggest that sP rats posses s a genetically determined, greater sensitivity to the motor impairing and sedative/hypnotic effects of ethanol than sNP rats. Although caution should be adopted before hypothesizing any comparison to humans, these results ma y feature sP rats as an experimental model of those subsets of human alcoho lics with initial high sensitivity to ethanol challenges. Finally, the resu lts of experiment 3 suggest a minimal involvement of the benzodiazepine and barbiturate recognition sites in the differential sensitivity to ethanol o f sP and sNP rats.