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dc.contributor.advisorAtkinson, Nigel (Nigel S.)en
dc.creatorAlhasan, Yazan Mahmouden
dc.date.accessioned2010-08-19T20:34:14Zen
dc.date.accessioned2010-08-19T20:34:24Zen
dc.date.available2010-08-19T20:34:14Zen
dc.date.available2010-08-19T20:34:24Zen
dc.date.issued2009-12en
dc.date.submittedDecember 2009en
dc.identifier.urihttp://hdl.handle.net/2152/ETD-UT-2009-12-552en
dc.descriptiontexten
dc.description.abstractProper neuronal function requires the preservation of appropriate neural excitability. An adaptive increase in neural excitability after exposure to agents that depress neuronal signaling blunts the sedative drug effects upon subsequent drug exposure. This adaptive response to drug exposure leads to changes in drug induced behaviors such as tolerance, withdrawal and addiction. Here I use Drosophila melanogaster to study the cellular and neuronal components which mediate behavioral tolerance to the anesthetic benzyl alcohol. I demonstrate that rapid tolerance to benzyl alcohol is a pharmacodynamic mechanism independent of drug metabolism. Furthermore, tolerance is a cell autonomous response which occurs in the absence of neural signaling. Using genetic and pharmacological manipulations I find the synapse to play an important role in the development of tolerance. In addition, the neural circuits that regulate arousal and sleep also alter benzyl alcohol sensitivity. Beyond previously described transcriptional mechanisms I find a post-translational role of the Ca2+-activated K+-channel, slowpoke in the development of tolerance. Finally, I explore a form of juvenile onset tolerance, which may have origins that differ from rapid tolerance. The implications of this study go beyond tolerance in Drosophila melanogaster to benzyl alcohol and can shed light on human drug tolerance, withdrawal and addiction.en
dc.format.mimetypeapplication/pdfen
dc.language.isoengen
dc.subjectAnestheticen
dc.subjectAnesthesiaen
dc.subjectToleranceen
dc.subjectSedationen
dc.subjectArousalen
dc.subjectAlcoholen
dc.subjectBenzyl alcoholen
dc.subjectMushroom bodiesen
dc.subjectEllipsoid bodyen
dc.subjectGal4en
dc.subjectIon channelen
dc.subjectSlowpokeen
dc.subjectBKen
dc.subjectShibireen
dc.subjectShien
dc.subjectSyxen
dc.subjectSyntaxinen
dc.subjectComatoseen
dc.subjectComten
dc.subjectParaen
dc.subjectParalyticen
dc.subjectLarvaen
dc.subjectDrosophilaen
dc.subjectmelanogasteren
dc.subjectHomeostasisen
dc.subjectNEMen
dc.subjectN-ethylmaleimideen
dc.subjectTemperature sensitiveen
dc.subjectConditional mutantsen
dc.subjectCell autonomousen
dc.subjectNeuronal excitabilityen
dc.subjectResistanceen
dc.subjectSensitizationen
dc.subjectVesicle fusionen
dc.subjectVesicle recyclingen
dc.subjectHeat shocken
dc.titleMechanisms of benzyl alcohol tolerance in Drosophila melanogasteren
dc.date.updated2010-08-19T20:34:24Zen
dc.contributor.committeeMemberZakon, Harold H.en
dc.contributor.committeeMemberGonzales, Rueben A.en
dc.contributor.committeeMemberSinger, Michael C.en
dc.contributor.committeeMemberBergeson, Susan E.en
dc.type.genrethesisen
thesis.degree.departmentNeuroscience, Institute foren
thesis.degree.disciplineNeuroscienceen
thesis.degree.grantorThe University of Texas at Austinen
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen


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