Medial prefrontal cortical extracellular dopamine responses after acutely experimenter-administered or orally self-administered ethanol

dc.contributor.advisorGonzales, Rueben Anthony
dc.creatorSchier, Christina Joanneen
dc.date.accessioned2013-11-11T21:37:22Zen
dc.date.issued2012-12en
dc.date.submittedDecember 2012en
dc.date.updated2013-11-11T21:37:23Zen
dc.descriptiontexten
dc.description.abstractDopamine signaling in the prefrontal cortex is thought to play a role in ethanol abuse. However, little is known about how ethanol affects dopamine signaling in the region. There are a few rodent studies regarding the matter, but both the pharmacological effects of ethanol and the effects of self-administered ethanol on extracellular dopamine in the medial prefrontal cortex remain unclear. The goal of the studies conducted for this dissertation is to clarify these relationships. To accomplish this, we monitored both dialysate dopamine and ethanol concentrations in the medial prefrontal cortex of Long Evans rats while an experimenter administered or a rat operantly self-administered ethanol. In naïve rats, dopamine dose-dependently increased after the intravenous infusions of a 10% ethanol solution, while no changes were noted after saline infusions. In rats trained to orally self-administer drinking solutions, dopamine transiently increased at the initiation of consumption in both ethanol-plus-sucrose- and sucrose-solution-consuming rats. Dopamine concentrations remained significantly elevated for the entire 21-minute drinking period in the ethanol-plus-sucrose-consuming group and for the first seven minutes of the drink period in the sucrose-consuming group. Additionally, in the ethanol-plus-sucrose-consuming group, dialysate ethanol concentrations were lowest at the initiation of drinking and then slowly increased, peaking 35 minutes after drinking commenced. Taken together, these data suggest that the mesocortical dopamine system is responsive to acute, intravenous and repeatedly, orally, self-administered ethanol. It appears that direct pharmacological effects of ethanol were responsible for the dopamine increase after acute, ethanol administration. Furthermore, while is it possible that the direct pharmacological effects of ethanol also bolstered the dopamine response seen after ethanol self-administration, we cannot firmly conclude by what mechanism ethanol elicited the differences. Overall, our clarifying and novel results support a role for the mesocortical dopamine system in ethanol abuse, which deserves continued investigation. In addition to completing the two aforementioned data studies, we also published the methods we use to monitor dialysate ethanol concentrations, in a specific brain region, during ethanol self-administration in a video-methods journal. The methods are presented in both a detailed written protocol, as well as a video demonstrating how to perform the procedures.en
dc.description.departmentPharmacyen
dc.embargo.lift12/1/2013en
dc.embargo.terms12/1/2013en
dc.format.mimetypeapplication/pdfen
dc.identifier.urihttp://hdl.handle.net/2152/22113en
dc.language.isoen_USen
dc.subjectEthanolen
dc.subjectRaten
dc.subjectDopamineen
dc.subjectPrefrontal cortexen
dc.subjectMesocorticalen
dc.subjectAddictionen
dc.titleMedial prefrontal cortical extracellular dopamine responses after acutely experimenter-administered or orally self-administered ethanolen
thesis.degree.departmentPharmacyen
thesis.degree.disciplinePharmacyen
thesis.degree.grantorThe University of Texas at Austinen
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen
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