The effect of L-dopa on levels of uric acid in the striatum of the rat as measured by in vivo electrochemical detection and its implications for dopamine-adenosine interactions.
Item
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Title
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The effect of L-dopa on levels of uric acid in the striatum of the rat as measured by in vivo electrochemical detection and its implications for dopamine-adenosine interactions.
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Identifier
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AAI9119686
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identifier
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9119686
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Creator
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Togasaki, Daniel Minoru.
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Contributor
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Adviser: Peter J. Knott
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Date
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1991
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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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Biology, Neuroscience
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Abstract
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This study used in vivo electrochemical detection to examine the level of extracellular uric acid in the striatum and its relationship to circling behavior in male Sprague-Dawley rats. Electrochemical measurements were made with carbon paste electrodes and a BAS DCV-5 voltammetry controller using the technique of semidifferentiated linear sweep voltammetry to examine "Peak 2". Preliminary experiments optimized electrode construction techniques and methodology.;Electrodes were bilaterally implanted into the striata of rats that had undergone unilateral lesioning of their dopaminergic nigrostriatal neurons using 6-hydroxydopamine. Three days after surgery, the rats were monitored by simultaneously measuring circling behavior and Peak 2 height during 9 ten-minute sessions before and after injection of scL-dopa (three hours total). scL-Dopa induced circling behavior away from the lesioned side and also an increase in the height of Peak 2 that was larger on the lesioned side. The amount of circling behavior correlated highly with the asymmetry in the Peak 2 changes, suggesting a strong relationship between them.;Experiments using HPLC techniques to monitor striatal neurochemistry showed, in lesioned rats, that scL-dopa increased turnover of dopamine in the striatum, but not serotonin.;Other experiments used an electrode/cannula assembly to monitor Peak 2 while simultaneously microinjecting substances into adjacent striatum. These experiments identified Peak 2 as uric acid and showed that its height was increased by microinjection of adenosine, suggesting that the uric acid is derived from local adenosine metabolism. scL-Dopa microinjection also caused an increase in Peak 2, indicating that it affects uric acid levels by a locally mediated mechanism. Further experiments using 2{dollar}\sp\prime{dollar}-deoxycoformycin, carbidopa, Ro4-4602, haloperidol, and apomorphine were inconclusive.;The use of in vivo electrochemical detection and electrode/cannula assemblies is discussed. The role of adenosine in striatal physiology and circling behavior is discussed regarding these results and possible clinical implications for Parkinson's Disease and Lesch-Nyhan Syndrome. The appendix includes a preliminary report of a study investigating the effect of dietary caffeine on Parkinson's Disease.;In summary, this study shows a relationship between striatal uric acid levels and circling behavior and suggests it is mediated by adenosine/dopamine interactions.
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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.
