The role of estrogen and progesterone in neurochemical, endocrinological and behavioral responses to acute cocaine.
Item
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Title
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The role of estrogen and progesterone in neurochemical, endocrinological and behavioral responses to acute cocaine.
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Identifier
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AAI3187441
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identifier
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3187441
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Creator
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Niyomchai, Tipyamol.
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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 | Health Sciences, Pharmacology
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Abstract
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Estrogen and progesterone have been shown to alter responses to cocaine. We hypothesize that the concentrations of the hormones, time between hormonal surges, hormonally-mediated molecular and neurochemical mechanisms, and hormonal impact on cocaine metabolism are all factors that contribute to cycle-related fluctuations in cocaine effects. Utilizing different hormonal replacement paradigms we indeed found that estrogen and progesterone modulate responses to cocaine in a complex manner. Although estrogen did not affect cocaine-induced ambulatory and rearing behaviors dose-dependently, it affected stereotypic behaviors regardless of cocaine administration (animals receiving 50 mug had higher stereotypic counts than did the OVX group). In contrast, progesterone affected rearing activity dose-dependently: 50 and 500 mug of progesterone inhibited, whereas 100 mug and 250 mug stimulated, rearing in response to cocaine. The duration of hormonal exposure is also an important factor in cocaine-induced alterations; short-term estrogen replacement decreased cocaine-induced ambulations. Short-term progesterone decreased rearing, whereas long-term progesterone decreased ambulations. However, preprodynorphin mRNA levels were increased in the caudate putamen of ovariectomized female rats pretreated with vehicle or a combination of estrogen and progesterone but not in ovariectomized female rats that were pretreated with either estrogen or progesterone alone. We also demonstrated that estrogen and progesterone either synergize to facilitate or antagonize to inhibit cocaine-induced behaviors. When progesterone was administered 1 and 48 hours after estrogen replacement, locomotor behavior was inhibited. On the other hand, when progesterone was administered 24 hours after estrogen replacement, behavior was enhanced. When animals were administered 50 mug E + 500 mug P (levels reflecting those observed during the late proestrus stage), total locomotor behavior was enhanced while levels of dopamine (DA) in the nucleus accumbens and the ratio of HVA to DA in the VTA were decreased. Administration of 10 mug E + 500 mug P (levels reflecting those observed during the diestrus stage) inhibited total locomotor activity and decreased baseline levels of DA. Estrogen and progesterone also affected cocaine pharmacokinetics: estrogen decreased brain levels of cocaine and norcocaine 30 minutes after cocaine administration in comparison to the group receiving vehicle at that time point and in progesterone-treated rats, levels of benzoylecgonine and ecgonine methylester were higher at 30 minutes post-administration than at 15 minutes. No changes were found in blood levels of the metabolites. These findings suggest that there are multi-faceted interactions between estrogen and progesterone in mediating the effects of cocaine.
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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.
