Inhibition of Metaphit-Induced
Audiogenic Seizures by APV in Rats
D. ŽIVANOVIČ, V. ŠUŠIČ, O.
STANOJLOVIČ
Department of Physiology, School of Medicine,
University of Belgrade, Belgrade, Yugoslavia
Received June 25, 1998
Accepted January 7, 1999
Summary
The influence of APV ((±)-2-amino-5-phosphonovaleric acid) on
EEG activity and behavior was studied on a model of epilepsy
induced by intraperitoneal administration of metaphit
(1-(1-(3-isothiocyanatophenyl)-cyclohexyl)-piperidine). Male
Wistar rats received an injection of metaphit (10 mg/kg) and
were subjected to intense audio stimulation (100±3 dB, 60 s) at
hourly intervals during the experiment. The seizures were
classified according to a four point scale ranging from 0 (no
seizure) to 3 (tonic convulsions). In our report we studied the
time course which revealed the maximum incidence and severity of
seizures 7-12 h after the injection (10 out of 12 rats, with
severity of 2.25±0.32). APV (0.05, 0.1, 0.2 and 0.3 m mol) was
injected intracerebroventricularly at the time of fully
developed convulsions. APV inhibited seizures in a
dose-dependent manner. The minimum dose, which completely
blocked seizures in all animals, was 0.3 m mol, while ED50 were
0.11, 0.10 and 0.07 m mol against running, clonus and tonus,
respectively. In contrast to behavioral inhibition of
convulsions, metaphit-provoked epileptiform activity was not
abolished by APV, and represented a prerequisite for the
reappearance of behavioral seizures. It is suggested that APV is
rather an anticonvulsant than an antiepileptic agent in this
model of epilepsy.
Key words
Rat · Metaphit · Audiogenic seizures · APV · EEG
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