Sex differences in behavioral and intracellular responses to cocaine.
Item
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Title
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Sex differences in behavioral and intracellular responses to cocaine.
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Identifier
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AAI3159241
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identifier
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3159241
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Creator
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Nazarian, Arbi.
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Contributor
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Adviser: 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 | Biology, Neuroscience | Psychology, Physiological
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Abstract
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Female rats are more sensitive to cocaine-induced behaviors than male rats. However, the underlying mechanisms involved in this sensitivity are not well understood. The purpose of this proposal is to assess the role of dopamine receptors (D1 and D2) and their related signal transduction pathway in the sex differences in cocaine-induced reward, locomotion, and sensitization. To study the role of D1 and D2 receptors in cocaine reward, a conditioned place preference (CPP) paradigm was utilized. Specifically, the D1 antagonist SCH 23390, and the D2 antagonist eticlopride were administered to male and female rats during cocaine conditioning to block the development of CPP. All doses of SCH 23390 blocked cocaine CPP in male rats, whereas in female rats, only the low and the moderate dose of the drug blocked cocaine CPP. Eticlopride, on the other hand, did not to block cocaine CPP in male or female rats.;To measure the role of signal transduction mechanisms in sex differences to cocaine, protein kinase A (PKA) and cAMP response element binding protein (CREB) levels were measured after an acute injection of cocaine. Female rats given acute cocaine demonstrated a longer lasting and more robust locomotor enhancement than male rats. Interestingly, female rats had higher basal levels of PKA in the nucleus accumbens (NAc) than male rats. After acute cocaine, accumbal CREB phosphorylation was enhanced in both sexes, but the enhancement was much shorter lasting in female rats than in male rats (5min vs. 30min). Cocaine did not alter CREB phosphorylation in the caudate-putamen (CPu) of either sex, nor were PKA levels changed in CPu or the NAc.;Sex differences after chronic cocaine administration was studied along with measurements of PKA and phosphorylated CREB. Overall, male rats developed sensitization, while female rats exhibited behavioral tolerance to cocaine-induced locomotor behaviors. No differences in PKA or phospho-CREB levels were detected in the NAc or CPu between chronic cocaine, acute cocaine, or saline treated male and female rats.;Based on the present findings, dopamine receptors have a limited role in the sex differences to cocaine's response, whereas intracellular signaling components appear to be contributing to the sex difference observed in the behavioral measurements.
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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.
