Induction of progesterone serum levels mediated the behavioral responses to cocaine through activation of progesterone receptors.
Item
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Title
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Induction of progesterone serum levels mediated the behavioral responses to cocaine through activation of progesterone receptors.
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Identifier
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AAI3187375
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identifier
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3187375
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Creator
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Wu, Hui-Bing (Katie).
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Contributor
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Advisers: Joseph Glick | Vanya Quinones-Jenab
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Date
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2005
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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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Although accumulating evidences suggest cocaine-induced behavioral sex differences, the mechanism of action remains unclear. The aim of this proposal is to delineate the underlying mechanism of actions at different levels.;At the behavioral level, we extended previous studies by demonstrating that sex differences occurred in certain aspects of cocaine-induced behavioral activation, development, and sensitization. Furthermore, we demonstrated that this sensitization effect maybe gonadal hormone mediated as cocaine-treated GDX female rats had similar ambulatory counts as cocaine-treated intact male rats.;At the endocrine level, female rats have an exaggerated HPA axis response compared with male rats. We extended this finding by demonstrating that chronic cocaine administration did not alter corticosterone plasma levels, indicating the possible development of tolerance of HPA activity.;RU 486, a progesterone receptor (PR) antagonist, significantly attenuated cocaine-induced ambulatory and rearing behaviors in males, while tamoxifen, an estrogen receptor (ER) antagonist, spared all aspects of locomotor measurements in both male and female rats. Taken together, our results suggest that ER may play a limited role, while PR activation is a necessary step in the cascades of events that may account for the behavioral and neuroendocrinological responses to acute cocaine administration.;At the receptor level, we found that PR protein levels and PR-DNA complex formation were differentially affected dose-dependently by cocaine. 15mg/kg of cocaine upregulated nuclear PR-A protein levels and PR-DNA complex, while 30 mg/kg of cocaine upregulated nuclear PR-A protein levels, but downregulated PR-DNA complex at a later time point. The results suggest that different doses of cocaine may activate different pathways, which in turn, may mediate the short- and long-term effects of progesterone. In addition, regardless of drug treatment or time course, whole cell extracts had no effect on PR protein or PR-DNA complex levels, suggesting that the receptor activation is internalized into the nucleus while little or no activity occurs in the cytoplasm.;Taken together, the effects of cocaine on circulating hormone levels, protein levels, and functional DNA complexes may play a crucial role in cocaine-induced behavioral sex differences.
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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.
