Contingent drug tolerance: differential tolerance to the anticonvulsant, hypothermic, and ataxic effects of ethanol.

The kindled-convulsion model of epilepsy was used to study contingent tolerance to ethanol's (1.5 g/kg; IP) anticonvulsant, hypothermic, and ataxic effects in adult male rats. In the present experiments, three groups of amygdala-kindled rats received a series of bidaily (one every 48 h) convulsive stimulations: one group received ethanol 1 h before each stimulation; one group received ethanol 1 h after each stimulation; and another group served as the saline control. Tolerance to ethanol's anticonvulsant effect (Experiments 1 and 2) was greatest in those rats that received ethanol before each convulsive stimulation; whereas, tolerance to ethanol's hypothermic (Experiments 1 and 2) and ataxic (Experiments 2) effects developed in both groups that received ethanol. These results were predicted on the basis of the drug-effect theory of drug tolerance: the theory that functional drug tolerance is an adaptation to the disruptive effects of drugs on concurrent patterns of neural activity, not to drug exposure per se.