Development of a New Pharmacological Seizure Model: Effects of Anticonvulsants on Cortical‐and Amygdala‐Kindled Seizures in the Rat

Abstract

The potency of eight standard anticonvulsants was tested in dose-response studies on kindled rats. Animals with either amygdala- or cortical-generalized seizures were used, and the effects of drugs were assessed on: (1) amygdala focal activity; (2) cortical focal activity; and (3) the generalized convulsion triggered from either focus. Ethosuximide, which is used against absence attacks, was not effective at subtoxic levels against any type of kindled seizure. The seven other drugs, all of which are effective against tonic-clonic seizures, were found to be: (a) most potent against generalized convulsive seizures; (b) slightly less potent against cortical focal activity; and (c) only partially effective against amygdala focal activity even at high (toxic) doses. The effect of these drugs on kindled seizures closely parallels their known clinical effects against (respectively) tonic-clonic, simple partial, and complex partial attacks. It is concluded that the kindling preparation could provide new pharmacological models for several different types of clinical seizure. Its most important use, however, is likely to be as a model for complex partial seizures, since there is at present no satisfactory pharmacological model for these common and drug-resistant attacks.

The Anticonvulsant Effects of Progesterone and 5α‐dihydroprogesterone on Amygdala‐kindled Seizures in Rats

“…The criterion of "total suppression" was chosen for the amygdala focus, because this aspect of the kindled amygdala seizure models complex partial seizures (8). Shortening of the afterdischarge-which is generally seen before the focus is suppressed appears to reflect suppression of discharge in extrafocal circuits.…”

“…Progesterone dose-response experiments were then initiated, by using a modification of the test paradigm of Albright and Burnham (8). Eleven female Wistar rats that had reached criterion were injected s.c. on every second day with one of the following doses of progesterone: 0, 10, 20, 40, 80, 120, or 160 mg/kg.…”

“…It is the focal amygdaloid EEG afterdischarge that models complex partial seizures. The generalized components of generalized seizures model tonic-clonic seizures (8).…”

“…The amygdala kindling model is a model of complex partial seizures with secondary generalization (8,9). Complex partial epilepsy is the most common type of epilepsy in adults, and it is often drug resistant (10).…”

Mood stabilizer psychopharmacology

“…The clinical efficacy of carbamazepine in the treatment of acute mania was first reported by Takezaki and Hanaoka (1971) in a small open trial [227], followed by a larger open trail by Okuma and colleagues (1975) [228]. The subsequent demonstration of carbamazepine's optimal usefulness against amygdala vs. cortical-kindled seizures [229], and the development of the kindling model of recurrent affective illness by Post, led to a more systematic investigation of its efficacy in recurrent affective disorders. Ballenger and Post reported the first controlled studies of carbamazepine efficacy in acute mania [230] in 1978, after which a number of studies have replicated this finding [23].…”