Behavioral and electrical correlates of absence seizures induced by thalamic stimulation in juvenile rhesus monkeys with frontal aluminum hydroxide implants: a pharmacologic evaluation

Abstract

A new method for producing electro-clinical correlates of absence seizures (petit mal epilepsy) in conscious juvenile rhesus monkeys is described. A behavioral arrest reaction associated with concomitant 2 ½ to 3 Hz spike and wave electroencephalograph (EEG) after discharge pattern, was obtained by thalamic stimulation in monkeys with bilaterally symmetric aluminum hydroxide (Al(OH)₃) lesions in anterior premotor cortical areas. The characteristic behavioral and EEC features associated with absence seizures appeared reproducibly, 63 ± 5 days after aluminum hydroxide cortical implantation. This test system distinguishes between anticonvulsants that are effective in generalized seizures of the absence type and anticonvulsant drugs that are effective in focal seizures. Clinically useful antiabsence drugs, such as ethosuximide, sodium valproate, clonazepam, and trimethadione, are effective in this model. Diphenylhydantoin, which is contraindicated in absence states, increases the spike and wave after-discharge pattern. The limitations, advantages, and potential usefulness of this model in predicting anti-absence activity as well as the incidence of side effects of new drugs is discussed.