Steroid hormone effects on cocaine-induced alterations in ovariectomized Fischer rats.
Item
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Title
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Steroid hormone effects on cocaine-induced alterations in ovariectomized Fischer rats.
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Identifier
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AAI9986366
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identifier
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9986366
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Creator
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Perrotti, Linda Irene.
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Contributor
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Adviser: Vanya Quinones
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Date
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2000
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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 a variety of pharmacological actions; however, its major effect is the inhibition of the reuptake of neuronal monoamines. Interestingly, there are sex differences and differences across the reproductive cycle of females in use and abuse of cocaine as well as in the behavioral and subjective responses to it's administration. The complex endocrinological profile of females may be involved in these sex and reproductive cycle differences. Estrogen and progesterone function in the brain to regulate neuronal activity and influence behavior. Due to the modulating effects of estrogen and progesterone on the CNS, these hormones may be an integral part of the cascade of events that are involved in cocaine's actions in the CNS. It is not clear what role(s) each of these hormones play individually or in combination in cocaine-induced subjective and physiological alterations. These investigations were conducted to understand the role(s) of these hormones on cocaine-induced alterations. This work shows that there is an interaction between ovarian hormones and cocaine on cocaine-induced behavioral, neurochemical, and molecular alterations. Modulation of the endocrine system, HPA activation and progesterone levels were observed in response to cocaine treatment. Estrogen modulated cocaine-induced alterations at the behavioral and molecular levels; chronic estrogen treatment caused sensitization of the locomotor response to cocaine and caused increases in plasma corticosterone levels after chronic cocaine administration. Progesterone alone did not alter the locomotor or stereotypic behavioral responses to cocaine. But the time of administration of progesterone relative to estrogen administration affected the behavioral response to cocaine; progesterone administered 24 hours after estrogen enhanced cocaine-induced increases in locomotor behaviors. However, progesterone administered 43--46 hours after estrogen decreased cocaine-induced increases in locomotion. The co-administration of progesterone and cocaine increased levels of 5-HT in the medial prefrontal cortex. Additionally, estrogen and progesterone and cocaine administration affected dynorphin expression in the opioid system. These results suggest that the interactions between ovarian hormones and cocaine may be the basis of gender and reproductive cycle differences in response to cocaine. Additionally, the stage of the cycle or use of steroid-based contraceptives at the time of cocaine administration may influence the effects of cocaine on brain functioning.
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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.
