Sodium pentobarbital-induced cross-tolerance to ethanol is learned in the rat.

Initially, rats were trained to walk on a treadmill to avoid footshock. Subsequently, rats given additional practice while pentobarbital-intoxicated became cross-tolerant to ethanol. However, rats given equivalent doses of pentobarbital after practice did not become cross-tolerant, nor did saline-vehicle controls. These results challenge the theories of cross-tolerance which are based exclusively upon cellular adaptations to pharmacological stimulation of drug-responsive neurons. That all of the cross-tolerance measured was attributable to the intoxicated practice suggests that this observed cross-tolerance was mediated by some form of learning.