Intraperitoneal injection of
ethanol (1-2 g/kg) and
chlordiazepoxide (2-16 mg/kg) suppressed susceptibility to audiogenically induced, clonic-
tonic seizures and antagonized forelimb
tremor in rats undergoing
ethanol withdrawal, 30 min
after treatment. However, a smaller dose of
ethanol (0.5 g/kg) actually increased clonic seizure frequency, suggesting that
ethanol exerts a biphasic proconvulsant/
anticonvulsant action. Direct activation of
gamma-aminobutyric acid (
GABA) receptors by intracisternal administration of
GABA (100-1000 micrograms),
muscimol (0.3-1.0 micrograms) or 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (
THIP) (0.3-3.0 micrograms) 5 to 10 min before testing also reduced susceptibility to audiogenic clonic-
tonic seizures. In sharp contrast to these
anticonvulsant actions,
GABA,
muscimol and
THIP had no effect on withdrawal-induced forelimb
tremors. Blockade of
GABA uptake with 1-2,4-diaminobutyric
acid (300 and 600 mg/kg i.p.) and inhibition of
GABA transaminase with
aminooxyacetic acid (12.5 and 25.0 mg/kg i.p.) both reduced susceptibility to
seizures. However,
anticonvulsant doses of these two drugs, unlike
GABA,
muscimol and
THIP, also reduced forelimb
tremor. Three other
GABA transaminase inhibitors,
gamma-vinyl GABA (450 and 900 mg/kg i.p.),
gamma-acetylenic GABA (50-150 mg/kg i.p.) and
ethanolamine-O-sulfate (250-750 mg/kg i.p.), were inactive against
ethanol withdrawal audiogenic
seizures and forelimb
tremors. These results indicate that direct
GABA receptor activation can selectively suppress one type of
ethanol withdrawal response (i.e., audiogenic seizure susceptibility) while failing to influence another (forelimb
tremors).