期刊
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
卷 25, 期 3, 页码 478-483出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1111/j.1530-0277.2001.tb02238.x
关键词
GABA(A) receptors; SS mice; LS mice; microsacs; chloride uptake
资金
- NIAAA NIH HHS [R01 AA03972] Funding Source: Medline
Background: SS and LS mice have been used to explore the genetic and neurochemical bases for differences in sensitivity to ethanol. The present study investigated the effects of ethanol on GABA, receptor function in microsacs from these genotypes. The purpose was to test a key element of the hypothesis that differences between these lines in sensitivity to ethanol-induced enhancement of GABA, receptor function underlie their selected differences in sensitivity to ethanol-induced loss of righting reflex (LORR). Methods: The effects of ethanol on GABA-activated Cl-36(-) uptake in brain membranes (microsacs) isolated from male SS and LS mice were tested using a chloride nux filtration assay. Results: Ethanol significantly enhanced GABA-activated Cl-36(-) uptake in SS microsacs at concentrations of 100-300 mM. Ethanol did not significantly affect GABA-activated chloride uptake in this preparation at concentrations of 25 and 50 mM. Ethanol significantly enhanced GABA-activated Cl-36(-) uptake in LS microsacs at concentrations of 25-100 mM, but not at 200 mM. Conclusion: The present studies are the first to show a statistically significant effect of ethanol on GABA-activated chloride uptake in both SS and LS mice with a clear difference between the genotypes in threshold. The relative threshold differences between SS and LS microsacs in sensitivity to ethanol indicate that selection for resistance to ethanol-induced LORR in SS mice has shifted the ethanol-GABA, receptor concentration-response curve to the right. The findings add key evidence that supports a cause-effect relationship between sensitivity to ethanol-induced potentiation of GABA, receptor function and genetically determined sensitivity to ethanol's behavioral effects.
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