Acute functional tolerance to the motor impairment effects of di-n-propylacetate.

Rats were trained to run treadmill fashion along a moving belt to avoid electric shock. After stabilization of performance, the effects of the anticonvulsant di-n-propylacetate (DPA; 100, 200 and 400 mg/kg) on treadmill locomotion were measured. Disturbances in gait and balance were reflected by an increased time off belt in a dose-related manner. In addition, animals showed a progressive improvement over the 3 two-min trials. A second experiment which measured the effects of 300 mg/kg DPA either 5 or 20 min postinjection revealed that the progressive improvement noted in the first experiment was not due to a diminished drug concentration or to an increased exposure to the drug. Thus, acute functional tolerance to the performance decrement produced by DPA appears to depend upon behavioural processes which enable an animal to overcome the drug-induced functional deficit by practicing the task while in the drug state.