The role of bicuculline, aminooxyacetic acid and gabaculine in the modulation of ethanol-induced motor impairment.
Ethanol's intoxicating effects may result from ethanol-induced changes in central gamma-aminobutyric acid (GABA) mechanisms. To further test this hypothesis, mice were pretreated with bicuculline (1 mg/kg s.c.), aminooxyacetic acid (15, 20, 25 or 30 mg/kg i.p.) or gabaculine (20 or 40 mg/kg i.p.). Following pretreatment, 20% ethanol (2.25 g/kg i.p.) was administered and rolling roller performance evaluated. All ethanol-treated control animals showed lack of rolling roller performance at 5 min post ethanol but regained rolling roller performance by 35 min. Only 42% of the bicuculline pretreated mice demonstrated lack of rolling roller performance at 5 min post ethanol and all regained rolling roller performance by 15 min. Impairment of rolling roller performance by ethanol was potentiated by aminooxyacetic acid in a dose-dependent manner. Aminooxyacetic acid (25 and 30 mg/kg doses) slowed blood ethanol disappearance although analysis of blood ethanol disappearance and motor impairment curves indicated that aminooxyacetic acid potentiation of ethanol-induced rolling roller performance impairment cannot be attributed solely to aminooxyacetic acid's effect on blood ethanol levels. Gabaculine also potentiated ethanol's impairment of rolling roller performance but was more effective than aminooxyacetic acid in slowing ethanol disappearance, suggesting that in comparison to aminooxyacetic acid, alteration of ethanol metabolism plays a greater role in gabaculine's potentiation of ethanol-induced motor impairment.
Hinko
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College of Pharmacy, University of Toledo, OH 43606.
Rozanov
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D000085:Acetates / Q000494:pharmacology*; D000625:Aminooxyacetic Acid / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D000431:Ethanol / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D051379:Mice; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects*
D000085:Acetates; D003509:Cyclohexanecarboxylic Acids; D000625:Aminooxyacetic Acid; C012987:gabaculine; D000431:Ethanol; D001640:Bicuculline