Barbiturate anesthesia and alcohol tolerance in a rat model.

Anesthetic responses to a variety of barbiturates were examined in adult male rats rendered alcohol-tolerant by administration of an ethanol-containing balanced liquid diet for 3 weeks. Within 9 hours of withdrawing the diets, groups of 10-15 ethanol-fed rats and pair-fed controls were injected intraperitoneally with one of the following drug/dose combinations: thiamylal 20, 40, or 60 mg/kg; methohexital 10, 20, or 40 mg/kg; secobarbital 20, 30, or 40 mg/kg; pentobarbital 10, 20, or 40 mg/kg; or phenobarbital 80, 120, or 160 mg/kg. Each animal was monitored for time to loss of righting reflex (onset of anesthesia), absence of response to a painful stimulus (analgesia), and sleeping time (duration of anesthesia). None of these three anesthetic responses differed significantly in ethanol-fed and control rats with any dose of thiamylal, methohexital, or secobarbital. In contrast, all three responses were significantly less in rats given the middle dose of pentobarbital (20 mg/kg) than they were in control rats. Onset and duration of anesthesia were also shorter with the middle dose of phenobarbital (120 mg/kg), but analgesia was not. The results of this study, in combination with others, suggest that 1) cross-tolerance to anesthetic effects of barbiturates in ethanol-tolerant rats is not uniform with all barbiturates: and 2) because shorter-acting barbiturates show negligible cross-tolerance with alcohol, higher doses of these agents may not be required for satisfactory anesthesia in chronically alcoholic humans.