GABA turnover in the brain of rat lines developed for differential ethanol-induced motor impairment.
The role of GABAergic neurons in the differential sensitivity to ethanol between the AT (Alcohol Tolerant) and ANT (Alcohol Nontolerant) rat lines developed for low and high degree of motor impairment from ethanol, was studied by comparing the effect of ethanol (2 or 4 g/kg, IP) on GABA turnover in different regions of the brain in these rat lines. GABA turnover was estimated from the accumulation of GABA after inhibition of GABA aminotransferase with aminooxyacetic acid (AOAA, 50 mg/kg, IP) given 10 min after administration of ethanol. The rats were killed two hours after the AOAA treatment with focused microwaves. The concentrations of GABA, aspartate, glutamate, glutamine and taurine were analyzed with HPLC. The saline-treated ANT rats were found to have a higher concentration of GABA in the striatum and a higher rate of GABA accumulation in the cerebellum than the AT rats. Ethanol suppressed the accumulation of GABA in both lines, but the suppression was significantly greater in the AT rats than in the ANT rats. In specific regions, this line difference was significant in the cerebral cortex and cerebellum with the higher ethanol dose. No line differences were found in the brain or tail blood ethanol concentration. AOAA increased the concentration of glutamine, decreased that of aspartate and glutamate, and did not modify that of taurine. The AOAA-induced changes in the concentrations of these amino acids were, however, minor relative to those found in the concentrations of GABA. The results that GABAergic mechanisms are involved in the differential sensitivity to the motor-impairing effects of ethanol between the AT and ANT rats.
Hellevuo
K
K
Research Laboratories, Alko Ltd., Helsinki, Finland.
Kiianmaa
K
K
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D004361:Drug Tolerance; D000431:Ethanol / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D005971:Glutamates / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013654:Taurine / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005971:Glutamates; D005973:Glutamine; D013654:Taurine; D001224:Aspartic Acid; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase