Behavioral toxicity of chronic ethosuximide and sodium valproate treatment in the epileptic baboon, Papio papio.

The purpose of this study was to assess the effects of chronic administration of gradually increasing doses of the anti-petit mal agents, ethosuximide (15-60 mg/kg/day) and valproic acid (7.5-240 mg/kg/day) on the performance of incremental repeated acquisition and incremental fixed-ratio tasks in the epileptic baboon, Papio papio. At approximately equipotent anticonvulsant doses, ethosuximide (45-60 mg/kg/day) was more behaviorally toxic than valproic acid (7.5-60 mg/kg/day), as determined by the ability of each drug to suppress the incremental repeated acquisition of behavioral chains. The behavioral deficits induced by ethosuximide (60 mg/kg/day) were still present 8 weeks after cessation of drug treatment in two of four animals. Evidence of enhanced acquisition of behavioral chains (decreases in errors) was noted in two of six animals during chronic treatment with valproic acid at a dose of 60 mg/kg/day but was never seen during chronic treatment with ethosuximide. Responding under an incremental fixed-ratio schedule of reinforcement was only affected minimally by either drug. These data suggest that 1) cognitive processes are more vulnerable to disruption by chronic ethosuximide administration than they are to chronic valproic acid administration, 2) performance under the more complex incremental repeated acquisition schedule is more sensitive to disruption than that under an incremental fixed-ratio schedule and 3) the effects of ethosuximide and valproic acid on performance under the incremental repeated acquisition schedule are not due to decreases in motivation or ability to manipulate the response levers.