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dc.creatorWallace, Kathleen Allison
dc.date.accessioned2012-06-07T22:51:00Z
dc.date.available2012-06-07T22:51:00Z
dc.date.created1997
dc.date.issued1997
dc.identifier.urihttp://hdl.handle.net/1969.1/ETD-TAMU-1997-THESIS-W154
dc.descriptionDue to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to digital@library.tamu.edu, referencing the URI of the item.en
dc.descriptionIncludes bibliographical references: 63-70.en
dc.descriptionIssued also on microfiche from Lange Micrographics.en
dc.description.abstractFunctional tolerance to ethanol and physical dependence are thought to involve central nervous system (CNS) adaptive changes in the function of neurotransmitter systems which resist the initial intoxicating actions of ethanol. Increasing evidence suggests that the y-aminobutyric acid typeA(GABA,) receptor is one target of ethanol where such adaptive changes by the CNS may occur. Adaptation could occur by downregulation of GABAAreceptor number or uncoupling of the GABAAreceptor sensitivity to ethanol and related CNS depressants. These agents which show cross-tolerance and dependence with ethanol are allosteric modulators at the GABAAreceptor. Uncoupling is the decrease in the activity of an allosteric modulator at the receptor without a change in receptor number after prolonged exposure to either the agonist or allosteric modulator. Varying results have been obtained when looking at uncoupling at the GABAAreceptor with chronic drug treatment. The goal of this project was to determine-tine whether allosteric potentiation of GABAAreceptors by a benzodiazepine, a novel anticonvulsant or a neurosteroid is uncoupled by chronic ethanol treatment which may contribute to functional tolerance and physical dependence. Chronic ethanol was not found to induce an uncoupling of the potentiation seen with rnidazolam (0. I and 1. 0 liM), loreclezole (10 [uM), or allopregnanolone (0. I uM) to 3 uM GABA. However, the higher concentration of allopregnanolone (1.0 [uM) did show potentiation of the 3 uM GABA response in the chronically ethanol treated cells. In contrast, an increased potentiation was seen with midazolam (0. I uM) and GABA (0. I uM) in the ethanol treated cells. No potentiation was seen of 30 liM GABA response with any of the allosteric modulators tested. Therefore, it does not appear that chronic ethanol uncoupled potentiation of loreciezole or 0. I [uM allopregnanolone acting by general allosteric mechanisms. However, the higher (1 [uM concentration of allopregnanolone, which is thought to be capable of directly activating the GABAAreceptor, did show uncoupling of potentiation with cells chronically exposed to ethanol; this finding is consistent with an adaptive change in GABAAreceptor function.en
dc.format.mediumelectronicen
dc.format.mimetypeapplication/pdf
dc.language.isoen_US
dc.publisherTexas A&M University
dc.rightsThis thesis was part of a retrospective digitization project authorized by the Texas A&M University Libraries in 2008. Copyright remains vested with the author(s). It is the user's responsibility to secure permission from the copyright holder(s) for re-use of the work beyond the provision of Fair Use.en
dc.subjectmedical sciences.en
dc.subjectMajor medical sciences.en
dc.titleUncoupling at the GABA(A) receptor with chronic ethanol in the rat medial septum/diagonal band (MS/DB)en
dc.typeThesisen
thesis.degree.disciplinemedical sciencesen
thesis.degree.nameM.S.en
thesis.degree.levelMastersen
dc.type.genrethesisen
dc.type.materialtexten
dc.format.digitalOriginreformatted digitalen


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