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dc.contributor.advisorAtkinson, Nigel (Nigel S.)*
dc.creatorAlhasan, Yazan Mahmoud
dc.date.accessioned2010-08-19T20:34:14Z
dc.date.accessioned2010-08-19T20:34:24Z
dc.date.available2010-08-19T20:34:14Z
dc.date.available2010-08-19T20:34:24Z
dc.date.created2009-12*
dc.date.issued2010-08-19
dc.date.submittedDecember 2009
dc.identifier.urihttp://hdl.handle.net/2152/ETD-UT-2009-12-552
dc.descriptiontext
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.
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.subjectAnesthetic
dc.subjectAnesthesia
dc.subjectTolerance
dc.subjectSedation
dc.subjectArousal
dc.subjectAlcohol
dc.subjectBenzyl alcohol
dc.subjectMushroom bodies
dc.subjectEllipsoid body
dc.subjectGal4
dc.subjectIon channel
dc.subjectSlowpoke
dc.subjectBK
dc.subjectShibire
dc.subjectShi
dc.subjectSyx
dc.subjectSyntaxin
dc.subjectComatose
dc.subjectComt
dc.subjectPara
dc.subjectParalytic
dc.subjectLarva
dc.subjectDrosophila
dc.subjectmelanogaster
dc.subjectHomeostasis
dc.subjectNEM
dc.subjectN-ethylmaleimide
dc.subjectTemperature sensitive
dc.subjectConditional mutants
dc.subjectCell autonomous
dc.subjectNeuronal excitability
dc.subjectResistance
dc.subjectSensitization
dc.subjectVesicle fusion
dc.subjectVesicle recycling
dc.subjectHeat shock
dc.titleMechanisms of benzyl alcohol tolerance in Drosophila melanogaster
dc.date.updated2010-08-19T20:34:24Z
dc.contributor.committeeMemberZakon, Harold H.*
dc.contributor.committeeMemberGonzales, Rueben A.*
dc.contributor.committeeMemberSinger, Michael C.*
dc.contributor.committeeMemberBergeson, Susan E.*
dc.type.genrethesis*
thesis.degree.departmentNeuroscience, Institute for
thesis.degree.disciplineNeuroscience
thesis.degree.grantorThe University of Texas at Austin
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy


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