Effects of phenytoin, phenobarbital, and valproic acid, alone and in selected combinations, on schedule-controlled behavior of rats.
The present study examined the effects of phenytoin (20, 30, 40, and 50 mg/kg), phenobarbital (10, 20, 30, and 40 mg/kg), and valproic acid (80, 120, 160, and 240 mg/kg), and those of phenobarbital (10 and 30 mg/kg) combined with phenytoin (20, 30, and 40 mg/kg) or valproic acid (80, 120, and 160 mg/kg), on the lever pressing of rats maintained under fixed-ratio and interresponse-time-greater-than-t schedules of food delivery. High doses of each individual drug significantly decreased mean group response (and reinforcement) rate under the fixed-ratio schedule. No dose of an individual agent significantly affected mean group response rate under the interresponse-time-greater-than-t schedule, although high doses of phenobarbital and valproic acid significantly reduced the mean group reinforcement rate under this schedule. When given in combination, phenobarbital and phenytoin and phenobarbital and valproic acid significantly reduced response (and reinforcement) rate under the fixed-ratio schedule and reinforcement rate under the interresponse-time-greater-than-t schedule. These reductions did not significantly differ in magnitude from those predicted by an additive model of drug interaction.
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004347:Drug Interactions; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology*; D010672:Phenytoin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012055:Reinforcement Schedule; D013997:Time Factors; D014635:Valproic Acid / Q000494:pharmacology*
D014635:Valproic Acid; D010672:Phenytoin; D010634:Phenobarbital