Behavioral analysis of the effects of 15 anticonvulsants in the amygdaloid kindled rat.

Abstract

One hundred-four Wistar rats were implanted with a bipolar electrode aimed at the right basolateral amygdala, and stimulated bipolarly twice daily (interval between stimulations 30 min) with a 150 μA, 4-s train of biphasic square-wave 1-ms pulses (100 pulses/s). Seventy-four animals developed a stimulation-induced clonic convulsion and, after further testing, 41 animals satisfied the stability criteria for entrance into the drug study. These criteria were three convulsions in response to three stimulations on the tenth stimulation day, and a convulsion after each stimulation for a period of 1 week on the drug-testing schedule. In the standardized test system, kindled rats were given two control stimulations; drug was then administered IP and, 30 min and 24 h later, further stimulation was given. After each stimulation the presence or absence of ipsilateral turning, closing of the ipsilateral eye, rearing up, falling over, facial clonus, forepaw clonus, hind paw clonus, hind paw tonus, and wet-shaking was assessed and the duration of forepaw clonus was measured. ID50 values (mg/kg) for inhibition of forepaw clonus 30 min after injection are: Clonazepam, 0.28; diazepam, 0.28; chlordiazepoxide, 0.86; carbamazepine, 5.0; meprobamate, 11.2; mesuximide, 17.5; depamide, 22.4; diphenylhydantoin, 31.5; phenacemide, 31.6; flunarizine, 42.8; mephenytoin, 64.7; valproate sodium, 64.7; acetazolamide, 80.0; trimethadione, 120.0; and primidone, 142.2. The ED50 doses for inhibition of the other seizure components were significantly correlated (P<0.01) with their ID50 value for forepaw clonus. These results suggest that the kindled rat is an appropriate and sensitive model with which to assess anticonvulsant drugs.