Protein kinase A and the forced swim test: A strain comparison.
Item
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Title
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Protein kinase A and the forced swim test: A strain comparison.
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Identifier
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AAI3205018
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identifier
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3205018
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Creator
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Rogacki, Nancy.
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Contributor
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Adviser: Gordon A. Barr
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Date
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2006
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Language
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English
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Publisher
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City University of New York.
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Subject
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Psychology, Psychobiology
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Abstract
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The second messenger cyclic AMP (cAMP) has been long documented as affected by antidepressant (AD) treatment. AD drugs typically take days to weeks to produce clinical efficacy. Although cAMP levels may be elevated by short-term AD administration, chronic AD's may be necessary to affect all of the components of the cAMP cascade, including the second messenger's receptor, protein kinase A (PKA). The first report to examine PKA binding in the human depressive brain was not published until 1997 (Lowther, Katona, Crompton, & Horton). PKA density was unaltered as demonstrated via saturation binding in five brain regions in depressive suicides, yet decreased in those currently taking AD drugs. No published account regarding a controlled study of the impact of chronic AD treatment on PKA density exists. Strain differences may exist for AD effects on biochemistry, as well as behavior. Two strains, one "normal" (Sprague-Dawley, SD) and one exhibiting depressive characteristics (Wistar Kyoto, WKY) were tested for changes in both measures as a result of subchronic and chronic AD treatment. These two strains were known previously to differ in their responses to the forced swim test (FST), an animal model of depression that detects AD activity with a high correlation to clinical efficacy. Firstly, the pharmacological profile of a single PKA receptor in two fractions, the cytosolic and particulate, of the frontal cortex was determined. Secondly, strain differences in PKA density and FST response to the clinically utilized AD's desipramine and bupropion were assessed. Alprazolam did not demonstrate an AD-like effect in the FST. The two rat strains differed in their control levels of FST behavior and PKA density, but not affinities. Only the SD strain showed PKA density changes at a low AD dose and only in the particulate fraction. The PKA density changes in both strains in the cytosolic fraction occurred only at the high dose of an AD, perhaps reflecting transcriptional processes. No consistent correlation between biochemistry and behavior was found. Both how the FST measures AD activity with clinical drug effect concordance and if AD effect can be fingerprinted via changes in PKA density remain unsolved.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
