ALCOHOL & EXPRESSION OF GABA/BZ RECEPTOR MESSINGER RNA

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Recent experimental studies have provided strong evidence that the gamma-aminobutyric acid/benzodiazepine (GABA/BZ) receptor mediates some of the effects of alcohol intoxication. The aim of this proposal is to study the effect of alcohol ingestion on the expression of GABA/BZ receptor subunit mRNAs in the mouse central nervous system. GABA/BZ receptor subunit mRNAs will be autoradiographically localized following Northern blot and in situ hybridization with subunit specific complementary [32p] and [35S]-oligonucleotide probes. These techniques will also be used to study the expression of GABA/BZ receptor subunit mRNA in granule cell cultures from developing normal mouse cerebella in the presence and absence of alcohol. The following experimental questions will be asked: What is the anatomical localization of subunit mRNAs coding for the alpha, beta and gamma subunits of the GABA/BZ receptor complex in adult murine central nervous system? How does the expression of subunit mRNAs coding for the alpha, beta and gamma subunits of the GABA/BZ receptor complex in the adult mouse brain change following chronic alcohol intoxication? Are there changes in the expression of MRNA coding for GABA/BZ receptor subunits in developing mouse brain in response to chronic maternal alcohol consumption? What is the difference in expression of GABA/BZ receptor subunit mRNAs in the CNS of ethanol-sensitive (LS) and ethanol-insensitive (SS) mice? How is the expression of GABA/BZ receptor subunit mRNAs in neuronal cultures of cerebellar granule cells affected by exposure to alcohol? The above studies will provide preliminary data of the effects of alcohol at the molecular genetic level in a specific neurotransmitter receptor system.