Facilitation of Amygdala Kindling Development and Kindled Seizures by Metaphit

Abstract

The effect of metaphit (a phencyclidine analogue with an acylating isothiocyanate) on kindling development and kindled seizures from amygdala was investigated in rats pretreated once with metaphit. Administration of a single dose of metaphit (10 or 20 mg/kg intraperitoneally i.p.) 4 h before the first electrical stimulation of the amygdala did not in itself induce seizures, but greatly facilitated development of behavioral seizures during kindling. This effect persisted throughout the whole process of electrical amygdala kindling without further dosing. In contrast, metaphit only transiently and modestly increased the growth of afterdischarge (AD) duration. In kindled rats, pretreatment with a single dose of metaphit (20 mg/kg) 8 h before the test stimulation reduced the threshold current required to elicit a stage 5 seizure and shortened the latency for bilateral forelimb clonus (BFC) without changing AD duration or BFC duration. The facilitation of kindling development and kindled seizures may be due to an excessive excitatory transmission by metaphit in the limbic seizure circuitry.

Interaction of Delta Sleep-inducing Peptide and Valproate on Metaphit Audiogenic Seizure Model in Rats

“…Our results are in agreement with Chen et al (1994), who demonstrated that the metaphit action in a single dose (10 and 20 mg/kg) after 8 h produced a maximal seizure activity, reduced the threshold current, and shortened the latency for clonus. The animal injected with metaphit would be ''primed,'' and when threshold is reached by a strong AGS in the animals would be convulsive, and it would facilitate synaptic potentials and accelerate limbic kindling enhancing excitability in forebrain, brainstem, and hippocampus (Chen et al 1994).…”

“…The animal injected with metaphit would be ''primed,'' and when threshold is reached by a strong AGS in the animals would be convulsive, and it would facilitate synaptic potentials and accelerate limbic kindling enhancing excitability in forebrain, brainstem, and hippocampus (Chen et al 1994).…”

“…As far as in 1945, Allen (1945) described reflex or stimulus-sensitive epilepsy and metaphit we used along with intense audiogenic stimulus represents reflex epilepsy model suitable for the research of anticonvulsive agents (Debler et al 1989;Chen et al 1994).…”