Bicuculline methiodide (0.5-3 nmol) and
picrotoxin (0.5-4 nmol) were injected uni- or bilaterally into the rat amygdala and the resulting behavioural, electroencephalographic and morphological alterations were studied. In rats treated unilaterally with lowest doses of either
bicuculline or
picrotoxin (0.5 and 1 nmol) increase in the locomotor activity, occasional
myoclonus of the hindlimbs and wet dog shakes were observed. At doses of 2-3 nmol, both gamma-aminobutyrate antagonists produced a sequence of repetitively occurring behavioural alterations including limbic gustatory automatisms,
tremor and
myoclonus of the forelimbs, head nodding and rearing, that developed over 15-30 min and built up progressively into the recurrent motor limbic
seizures lasting for 1-6 h. In animals injected bilaterally with either
bicuculline (0.5-3 nmol) or
picrotoxin (0.5-3 nmol) motor limbic
seizures rapidly developed into the
status epilepticus lasting for several hours.
Bicuculline and
picrotoxin produced both ictal and interictal epileptiform activity in the electroencephalogram. A spectrum of electroencephalographic changes consisted of high voltage fast activity, slow and fast voltage spiking, paraoxysmal bursts and periods of postictal depression. The earliest electrographic alterations appeared in the amygdala and then rapidly spread to cortical areas. Electrographic
seizures started 1-10 min after unilateral
injections of large doses of
bicuculline and pictrotoxin (2-4 nmol). Ictal periods lasted for 1-2 min, recurred every 5-10 min and were followed by periods of depression of the electrographic activity. Bilateral
injections of large doses of both gamma-aminobutyrate antagonists (2-3 nmol) resulted in the
status epilepticus. Morphological examination of frontal forebrain sections with light microscopy revealed a widespread damage to the amygdala, olfactory cortex, substantia nigra, thalamus, hippocampus and neocortex. Pretreatment of animals with
diazepam prevented the build-up of convulsive activity and brain damage produced by
bicuculline or
picrotoxin.
Muscimol retarded the appearance and shortened the duration of convulsive activity, but did not alter the sequence and intensity of
seizures. The results indicate that gamma-aminobutyrate antagonists,
bicuculline and
picrotoxin when directly applied to the amygdala can elicit in rats motor limbic
seizures, epileptic changes in the electroencephalogram indicative of repetitive limbic
seizures, and
status epilepticus accompanied by seizure-related brain damage.(ABSTRACT TRUNCATED AT 400 WORDS)