Effects of phenytoin and phenobarbital on schedule-controlled responding and seizure activity in the amygdala-kindled rat.

The purpose of the present study was to examine whether doses of phenytoin and phenobarbital that blocked kindled seizures in rats also disrupted operant behavior. Subjects initially were exposed to a kindling procedure in which repeated electrical stimulation of the amygdala evoked generalized seizures. After kindling, they were trained under a multiple fixed-ratio 30 interresponse-time-greater than 10-sec schedule of food delivery. Once each day, 6 days per week, 30-min exposures to this schedule were followed immediately by amygdaloid stimulation which occurred at no other time. Response rate, reinforcement rate and duration of forelimb clonus were recorded. When response rates were stable, 5 rats were tested with phenytoin (25, 50, 75 and 100 mg/kg) and 5 others were tested with phenobarbital (10, 25 and 40 mg/kg). Results indicated that doses of phenytoin that controlled kindled seizures also affected operant behavior. For this drug, the ED50 for forelimb clonus was 62 mg/kg. For response rate under the fixed-ratio and interresponse-time components, it was 48 and 58.2 mg/kg, respectively. Dose-response curves for the behavioral and antiseizure effects of phenobarbital were similar. However, for this drug the ED50 for forelimb clonus (18.9 mg/kg) was significantly lower than for response rate under the fixed ratio component (37.4 mg/kg).