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Science 20 July 1990:
Vol. 249. no. 4966, pp. 291 - 293
DOI: 10.1126/science.1695761
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Articles

Science, Vol 249, Issue 4966, 291-293
Copyright © 1990 by American Association for the Advancement of Science

articles

Genetic differences in the ethanol sensitivity of GABAA receptors expressed in Xenopus oocytes

KA Wafford, DM Burnett, TV Dunwiddie, and RA Harris

Department of Pharmacology, University of Colorado Health Sciences Center, Denver.

Animal lines selected for differences in drug sensitivity can be used to help determine the molecular basis of drug action. Long-sleep (LS) and short-sleep (SS) mice differ markedly in their genetic sensitivity to ethanol. To investigate the molecular basis for this difference, mRNA from brains of LS and SS mice was expressed in Xenopus oocytes and the ethanol sensitivity of gamma-aminobutyric acid A (GABAA)- and N-methyl D-aspartate (NMDA)-activated ion channels was tested. Ethanol facilitated GABA responses in oocytes injected with mRNA from LS mice but antagonized responses in oocytes injected with mRNA from SS animals. Ethanol inhibited NMDA responses equally in the two lines. Thus, genes coding for the GABAA receptor or associated proteins may be critical determinants of individual differences in ethanol sensitivity.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Ethanol Consumption during Early Pregnancy Alters the Disposition of Tangentially Migrating GABAergic Interneurons in the Fetal Cortex.
V. C. Cuzon, P. W. L. Yeh, Y. Yanagawa, K. Obata, and H. H. Yeh (2008)
J. Neurosci. 28, 1854-1864
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Haplotype-Based Localization of an Alcohol Dependence Gene to the 5q34 {gamma}-Aminobutyric Acid Type A Gene Cluster.
M. Radel, R. L. Vallejo, N. Iwata, R. Aragon, J. C. Long, M. Virkkunen, and D. Goldman (2005)
Arch Gen Psychiatry 62, 47-55
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Differential Effects of Ethanol on GABAA and Glycine Receptor-Mediated Synaptic Currents in Brain Stem Motoneurons.
J. Y. Sebe, E. D. Eggers, and A. J. Berger (2003)
J Neurophysiol 90, 870-875
   Abstract »    Full Text »    PDF »
Pharmacogenetics of Alcohol Response and Alcoholism: The Interplay of Genes and Environmental Factors in Thresholds for Alcoholism.
M. Radel and D. Goldman (2001)
Drug Metab. Dispos. 29, 489-494
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Ethanol: Novel Actions on Nerve Cell Physiology Explain Impaired Functions.
E. R. Korpi, R. Makela, and M. Uusi-Oukari (1998)
Physiology 13, 164-170
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Fyn-Kinase as a Determinant of Ethanol Sensitivity: Relation to NMDA-Receptor Function.
T. Miyakawa, T. Yagi, H. Kitazawa, M. Yasuda, N. Kawai, K. Tsuboi, and H. Niki (1997)
Science 278, 698-701
   Abstract »    Full Text »
Differential Ethanol Sensitivity of Subpopulations of GABAA Synapses Onto Rat Hippocampal CA1 Pyramidal Neurons.
J. L. Weiner, C. Gu, and T. V. Dunwiddie (1997)
J Neurophysiol 77, 1306-1312
   Abstract »    Full Text »    PDF »
Beta Adrenergic Sensitization of gamma -Aminobutyric Acid Receptors to Ethanol Involves a Cyclic AMP/Protein Kinase A Second-Messenger Mechanism.
R. K. Freund and M. R. Palmer (1997)
J. Pharmacol. Exp. Ther. 280, 1192-1200
   Abstract »    Full Text »
Genetic animal models of alcohol and drug abuse.
J. Crabbe, J. Belknap, and K. Buck (1994)
Science 264, 1715-1723
   Abstract »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)