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