Mechanisms of benzyl alcohol tolerance in Drosophila melanogaster


Mechanisms of benzyl alcohol tolerance in Drosophila melanogaster

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dc.contributor.advisor Atkinson, Nigel (Nigel S.)
dc.creator Alhasan, Yazan Mahmoud 2010-08-19T20:34:14Z 2010-08-19T20:34:24Z 2010-08-19T20:34:14Z 2010-08-19T20:34:24Z 2009-12 2010-08-19 December 2009
dc.description.abstract Proper 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.mimetype application/pdf
dc.language.iso eng
dc.subject Anesthetic
dc.subject Anesthesia
dc.subject Tolerance
dc.subject Sedation
dc.subject Arousal
dc.subject Alcohol
dc.subject Benzyl alcohol
dc.subject Mushroom bodies
dc.subject Ellipsoid body
dc.subject Gal4
dc.subject Ion channel
dc.subject Slowpoke
dc.subject BK
dc.subject Shibire
dc.subject Shi
dc.subject Syx
dc.subject Syntaxin
dc.subject Comatose
dc.subject Comt
dc.subject Para
dc.subject Paralytic
dc.subject Larva
dc.subject Drosophila
dc.subject melanogaster
dc.subject Homeostasis
dc.subject NEM
dc.subject N-ethylmaleimide
dc.subject Temperature sensitive
dc.subject Conditional mutants
dc.subject Cell autonomous
dc.subject Neuronal excitability
dc.subject Resistance
dc.subject Sensitization
dc.subject Vesicle fusion
dc.subject Vesicle recycling
dc.subject Heat shock
dc.title Mechanisms of benzyl alcohol tolerance in Drosophila melanogaster 2010-08-19T20:34:24Z
dc.contributor.committeeMember Zakon, Harold H.
dc.contributor.committeeMember Gonzales, Rueben A.
dc.contributor.committeeMember Singer, Michael C.
dc.contributor.committeeMember Bergeson, Susan E.
dc.type.genre thesis
dc.type.material text Neuroscience, Institute for Neuroscience The University of Texas at Austin Doctoral Doctor of Philosophy

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