DIFFERENTIAL SENSITIVITY OF ETHANOL WITHDRAWAL SIGNS IN THE RAT TO GAMMA-AMINOBUTYRIC ACID (GABA)MIMETICS - BLOCKADE OF AUDIOGENIC-SEIZURES BUT NOT FORELIMB TREMORS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 226  (3) , 720-725
Abstract
Injection of ethanol (1-2 g/kg i.p.) and chlordiazepoxide (2-16 mg/kg i.p.) suppressed susceptibility to audiogenically induced, clonic-tonic seizures and antagonized forelimb tremor in rats underoing ethanol withdrawal 30 min after treatment. 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 GABA receptors by intracisternal administration of GABA (100-1000 .mu.g), muscimol (0.3-1.0 .mu.g) or 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) (0.3-3.0 .mu.g) 5 to 10 min before testing also reduced susceptibility to audiogenic clonic-tonic seizures but had no effect on withdrawal-induced forelimb tremors. Blockade of GABA uptake with l-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. Anticonvulsant doses of these 2 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. Apparently, direct GABA receptor activation can selectively suppress 1 type of ethanol withdrawal response (i.e., audiogenic seizure susceptibility) while failing to influence another (forelimb tremors).