Neonatal visceral pain (NVP) is a severe problem affecting up to 12% of newborns in the United States. This unacceptably high statistic, and the fact that the changes in brain opioid systems elicited by NVP may have persistent pharmacological consequences into adulthood, suggests that NVP increases sensitivity to abuse-related effects of opioids across all stages of development. Despite the significance of this outcome, few studies exist to explain the influence of neonatal pain on subsequent developmental contributions to opioid pharmacology. In this dissertation, we examined the effects of NVP on the propensity to abuse morphine during development and the relationship of NVP to neuropharmacological changes to the mu, kappa, and delta opioid receptors in the cortex, thalamus, and brainstem as a potential underlying mechanism.
Questions raised within this dissertation were addressed using self-administration, drug discrimination, and locomotor sensitization to examine how NVP may increase susceptibility to abuse-related effects of morphine in a rat model. Next, assays to measure morphine analgesia, dependence, and withdrawal in rats were used to evaluate the predisposing effects of NVP across all developmental stages. Finally, the effects of NVP and its role in modulating µ, κ, and δ opioid receptor density and function in rat cortex, thalamus, and brainstem were assessed to predict the potential neuropharmacological changes produced by NVP.
The hypothesis explored here is that the changes in brain opioid systems elicited by NVP have persistent pharmacological consequences into adulthood, and that NVP increases sensitivity to abuse-related effects of opioids across development. Each year, NVP affects a significant number of newborns, and the current NVP treatment may predispose these neonates to drug abuse later in life. Therefore, data from these studies suggest meaningful mechanisms for changing the present standards for treating neonatal pain and stress. Such changes may allow these neonates to avoid developing a predisposition for abusing opioids. Because mean annual direct health care costs for opioid abuse exceeds $55.7 billion, understanding the underlying mechanisms behind events that potentially drive propensities for drug abuse would confer obvious benefits to human health.
|Advisor:||Fantegrossi, William E.|
|Commitee:||Carter, Lawrence P., Kilts, Clinton D., Prather, Paul P., Wessinger, William D.|
|School:||University of Arkansas for Medical Sciences|
|Department:||Interdisciplinary Biomedical Sciences|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 75/09(E), Dissertation Abstracts International|
|Subjects:||Neurosciences, Behavioral psychology, Pharmacology|
|Keywords:||Drug abuse, Drug discrimination, Morphine, Self-administration, Sprague dawley, Visceral pain|
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