Biphasic effects of ethanol tested with drug discrimination in HAD and LAD rats.

Seventh-generation selectively bred high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rats were trained to make differential responses for ethanol (0.75 g/kg, IP) and saline vehicle, following postadministration intervals (PI) of 2 min (HAD-2 and LAD-2 animals) and 30 min (HAD-30 and LAD-30 animals). ED50 values of 0.395 and 0.352 g/kg, respectively, for HAD-2 and LAD-2 animals and 0.269 and 0.314 g/kg, respectively, for HAD-30 and LAD-30 animals reflect the absence of any phenotypic difference for the discriminative stimulus effects of ethanol. HAD-2 animals were more responsive than LAD-2 animals to the stimulating effects of ethanol as measured by total response rates during training sessions. The differential ethanol response generalized to pentobarbital in all four groups but not to morphine, an alternative CNS depressant. The specific antagonist of 5-hydroxytryptamine3 receptors, 3-tropanyl-3,5-dichlorobenzoate (MDL 72222), up to doses of 14.0 mg/kg failed to antagonize the discriminative effects of ethanol. Ethanol sleep times did not differ between groups.