The effects of morphine treatment on intracellular signalling in the young rat.
Item
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Title
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The effects of morphine treatment on intracellular signalling in the young rat.
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Identifier
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AAI3187387
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identifier
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3187387
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Creator
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McPhie, Anika Ayo.
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Contributor
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Adviser: Gordon A. Barr
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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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The medicinal value and pleasurable effects of opiates have been known of for hundreds of years. Clinically, one major drawback of long-term opiate treatment is that it leads to tolerance and dependence. Many decades of research have gone into understanding these phenomena by studying the manifested behaviors in both human and animal models. A major finding has been that they occur and can be modeled in the young rodent. With the advancement of molecular techniques the IP3-DAG and cAMP/AC signal transduction pathways have been shown to regulate and be regulated by the opiate system. However, the majority of this work has been done in the adult organism, despite the fact that a constant population of human infants is exposed to opiates. These neonates and fetuses experience both tolerance and withdrawal, the latter of which is linked to increased morbidity and later cognitive problems. Because the mechanisms of tolerance and dependence differ between infant (PD7-14) and older animals (PD21+), the current experiments were conducted to determine if there are ontogenetic interactions between opiates and the IP3-DAG and cAMP/AC signal transduction systems. In the first set of experiments, the activity of the opioid receptors was pharmacologically blocked and the effects on withdrawal at PD7 were quantified. Results were similar to those found in the adult; the mu-opioid receptor played the predominant role in modulating withdrawal. Next, immunocytochemistry was employed to determine the neuroanatomical location of the activated gene c-fos during opiate withdrawal at PD7. Once again the results were similar to those found in adult rodents; increased Fos-like immunoreactivity was found in similar brain regions. Finally, the interaction between morphine and protein kinases was explored in two age groups, PD7 and PD21. Unlike the adult literature, pharmacological blockade of PKA and PKC had no inhibitory effect on withdrawal or tolerance. In addition, overall changes in levels of PKA and PKC were unaffected by morphine treatment at PD7 and PD21. Some of the findings of this dissertation are straight forward, while others are difficult to interpret. Further emphasizing the difficulty of accurately interpreting data obtained from studies using young rodents.
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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.
