Jpn. J. Pharmacol. 76 (4), 387-396 (1998)

Inhibition by gamma-Aminobutyric Acid System Activation of Epileptic Seizures in Spontaneously Epileptic Rats

Kenjiro Fukao (1), Toshihiko Momiyama (1,#), Kumatoshi Ishihara (2), Hisamitsu Ujihara (3), Yasuhiko Fujita (4), Kohtaro Taniyama (5), Tadao Serikawa (4) and Masashi Sasa (2,#)

(1) Department of Pharmacology and (4) Institute of Laboratory Animals, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan
(2) Department of Pharmacology, Hiroshima University School of Medicine, Hiroshima 734-8551, Japan
(3) Department of Neuropsychiatry, Kochi Medical School, Nankoku 783-8505, Japan
(5) Department of Pharmacology, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan
(#) Present address: 2nd Department of Physiology, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan
(*) To whom correspondence should be addressed.

Abstract: The effects of muscimol, a gamma-aminobutyric acid (GABA)A-receptor agonist, and aminooxyacetic acid (AOAA), an inhibitor of GABA-converting enzyme, on tonic and absence-like seizures in spontaneously epileptic rats (SER: zi/zi, tm/tm) were investigated to elucidate whether GABAergic function operates normally in these animals. Muscimol at doses of 1 and 3 mg/kg (i.p.) induced high-voltage slow waves in the cortical and hippocampal EEG of SER, although the behavioral observation suggested inhibition of absence-like seizures. Similar high-voltage slow waves were also observed in the cortical and hippocampal EEG of normal rats with muscimol (1 and 3 mg/kg). Tonic convulsions in SER were dose-dependently inhibited by muscimol. AOAA (3 and 10 mg/kg, i.v.) inhibited both tonic and absence-like seizures in SER, although there were no obvious changes in EEG pattern. The inhibitory effects of AOAA on tonic convulsions appeared more slowly and lasted longer than those on absence-like seizures. Cerebral, hippocampal and cerebellar GABA levels were significantly higher in SER than the normal Kyo:Wistar and zitter rat (zi/zi), which were both the parent strains. These findings suggest that GABA receptors and GABAergic neurons are functional in SER and that the GABA system is involved in the inhibition of both seizures.

Keywords: Spontaneously epileptic rat, gamma-Aminobutyric acid, Muscimol, Aminooxy-acetic acid, Epileptic seizure

Copyrightę The Japanese Pharmacological Society 1998

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