GABA mediation of the central effects of acute and chronic ethanol in mice.
In acute ethanol studies aminooxyacetic acid (AOAA) alone produced marked hypothermia although a test dose of ethanol was able to produce a further drop in body temperature in AOAA treated mice. Even though tolerance to ethanol-induced hypothermia was present in ethanol-dependent mice, AOAA administration was able to produce a further decrease in body temperature. Bicuculline potentiated ethanol-induced hypothermia in the acute studies but the tolerance to hypothermia which had developed in ethanol-dependent mice prevented the bicuculline-induced potentiation of ethanol hypothermia. AOAA markedly potentiated acute ethanol-induced motor incoordination whereas bicuculline had no effect. Although partial tolerance had developed to ethanol-induced motor incoordination in dependent mice, AOAA potentiated, whereas a lower dose of bicuculline antagonized, motor incoordination. In the acute studies ethanol had a biphasic effect on AOAA-induced GABA accumulation in the hypothalamus and corpus striatum: low doses prevented and a slightly higher dose was without effect on GABA accumulation. Ethanol-dependent mice were unable to respond to an AOAA-induced increase in GABA accumulation although basal levels of GABA were unaffected by chronic ethanol ingestion. The results show that brain GABA or GABA-mediated central mechanisms may be involved in the mediation of ethanol-induced motor incoordination but not hypothermia.
D000437:Alcoholism / Q000378:metabolism / Q000503:physiopathology*; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology*
D000625:Aminooxyacetic Acid; D000431:Ethanol; D005680:gamma-Aminobutyric Acid