Behavioral and Histopathological Analysis of Domoic Acid Administration in Marmosets

Abstract

To induce status epilepticus (SE) followed by the subsequent onset of spontaneous recurrent seizures, thus characterizing a new model of temporal lobe epilepsy in a nonhuman primate. Male and female marmosets (Callithrix jacchus) (n = 18), ages between 2 and 8 years, were injected with domoic acid (0.5-4 mg/kg, i.p.) or saline, and behaviorally assessed with regard to the presence of acutely induced seizures and for < or = 6 months for spontaneous seizures. Injection of doses ranging from 3.5 to 4 mg/kg either did not induce SE or resulted in fatal SE. Even a 5-min SE duration (SE blockade resulting from diazepam injection) proved lethal to marmosets within 1 h of domoate administration, regardless of intensive care and monitoring of the animals. Animals injected with doses ranging from 0.5 to 3 mg/kg that developed only a few minor convulsive signs were allowed a 6-month survival period for the assessment of spontaneous epileptic events. At the end of the experiment, 6-month period, or acute intoxication associated with SE induction, animals were deeply anesthetized and had their brains subjected to histologic processing for Nissl and delta-FosB. For the animals injected with domoate that did not develop SE (i.e., those that survived), we could not detect any behavioral signs of spontaneous epileptic seizures in the 6-month observation period, and only minor indications of neuropathologic changes (i.e., neuronal death) over Nissl-stained sections, as well as some small changes in the staining for delta-FosB in a few of the animals. Systemic administration of domoic acid to marmosets is not effective for the generation of a model of chronic temporal lobe epilepsy. Administration of domoic acid at doses that do not lead to SE also did not lead to the development of temporal lobe epilepsy or clear-cut behavioral changes over a 6-month period.