The role of the mesocorticolimbic dopamine system in the sexually dimorphic motor response to acute cocaine.
Item
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Title
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The role of the mesocorticolimbic dopamine system in the sexually dimorphic motor response to acute cocaine.
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Identifier
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AAI3127865
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identifier
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3127865
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Creator
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Festa, Eugene Daniel.
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Contributor
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Adviser: Vanya Quinones-Jenab
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Date
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2004
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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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Cocaine has been shown to increase locomotor behaviors in rats by altering monoaminergic transmission. It has been previously demonstrated that female rats have a more robust behavioral response to acute cocaine administration. The neurobiological mechanisms underlying these differences remain unclear. The aim of this proposal was to determine potential mechanisms underlying sexual disparities in motor behavior following acute cocaine administration. We found that cocaine injection frequency, dose, and metabolism may contribute to sex differences in cocaine-induced motor behavior. It was observed that cocaine was more potent in female rats and that the motor behavior of female rats persisted for a longer time frame as compared to male rats. Cocaine is also differentially metabolized in female rats; norcocaine levels in female rats were higher in the brain and serum, indicating that this bioactive metabolite may influence sex differences in cocaine-induced behaviors. These results may help in explaining the increased sensitivity to cocaine's addictive properties observed in human females.;We have also demonstrated that the dopaminergic response to acute cocaine administration is sexually dimorphic in the caudate putamen and the nucleus accumbens. Our neurochemical results suggest that autoregulatory feedback pathways modulating monoamine function in the striatum could be the basis for these disparities. In the dopamine system, we found that D1 receptors modulate cocaine-induced motor activity in a sex-dependent manner. Cocaine-induced motor activity in female rats was more sensitive to D1 receptor blockade. However, cocaine-induced alterations in D1 mRNA and binding levels were only observed in male rats. These results suggest that sex-dependent modulation of the D1 receptor system contributes to the differences observed in cocaine-induced motor activity, and to the initial cellular adaptations that occur following cocaine administration. Since pharamcological agents that target the dopamine system have long been the subject of treatment options for cocaine addiction, conceivably, sex should be an important variable in the development of therapeutics for drug addiction.
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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.
