GABAergic modulation of ethanol-induced motor impairment.
Direct or indirect pharmacological manipulation of gamma-aminobutyric acid (GABA) receptor activity was examined in relation to the motor incoordinating actions of ethanol in the rat. Ethanol (1.13-3.0 g/kg i.p.) caused a dose-dependent increase in the height of aerial righting. This motor impairment was increased selectively by intracisternal injection of the GABA agonists muscimol (0.10 microgram), 4,5,6,7-tetrahydroisoxazole(5,4-c) pyridin(3-ol) (1.0 microgram) and GABA (1000 micrograms). The GABA antagonist, bicuculline (1.0 and 5.0 micrograms intracisternally), reduced impairment. Thus, direct manipulation of GABA receptor activity modulated motor incoordination caused by ethanol. In addition, indirect-acting GABA-mimetics, such as gamma-acetylenic GABA (100 mg/kg i.p.), aminooxyacetic acid (50 mg/kg i.p.), ethanolamine-O-sulfate (250 mg/kg i.p.) and L-2,4-diaminobutyric acid (600 mg/kg i.p.) all potentiated the increase in the height of aerial righting caused by ethanol treatment. Failure of ethanol to modify the binding of [3H]muscimol to cerebral cortical membranes in vitro suggested there was no direct competition for GABA binding sites or facilitation of the binding of GABA to these sites by ethanol. Also, no simple relationship was observed between the degree of motor impairment caused by either ethanol or gamma-acetylenic GABA and changes in GABA concentration in three brain areas. Although GABAergic neurons may be involved in the mechanism underlying ethanol-induced depression of motor coordination, the interaction does not involve a direct activation of GABA receptors by ethanol.
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000480:Alkynes; D000613:Aminobutyrates / Q000494:pharmacology; D000614:Aminocaproates / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D000431:Ethanol / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D009048:Motor Skills / Q000187:drug effects*; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology*
D000480:Alkynes; D000613:Aminobutyrates; D000614:Aminocaproates; D007555:Isoxazoles; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D009118:Muscimol; C005959:2,4-diaminobutyric acid; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; C013785:4-amino-5-hexynoic acid; D000612:4-Aminobutyrate Transaminase; C015542:gaboxadol; D001640:Bicuculline