Opioid Receptors in Aging and Oxidative Stress

Simple item page
dc.contributor.advisorRatka, Anna
dc.contributor.committeeMemberSimpkins, James W.
dc.contributor.committeeMemberDillon, Glenn
dc.creatorRaut, Atul M.
dc.date.accessioned2019-08-22T21:34:15Z
dc.date.available2019-08-22T21:34:15Z
dc.date.issued2007-01-01
dc.date.submitted2013-09-30T06:24:05-07:00
dc.description.abstractRaut, Atul M., Opioid Receptors in Aging and Oxidative Stress. Doctor of Philosophy (Pharmacology and Neuroscience), January 2007, 181 pp, 4 illustrations, 21 figures, 159 titles. Oxidative stress has been implicated in aging and neurodegenerative disorders. Pain sensitivity and responses to opioids change with aging. The effect of aging and oxidative stress on opioid receptor system is not yet well understood. To study the effects of aging on pain sensitivity and opioid-induced antinociception, and to determine the possible association of oxidative stress with these pain parameters, in vivo studies were conducted. To further elucidate the effects of oxidative stress on opioid receptor proteins and their function, in vitro studies were carried out. The effects of aging on pain sensitivity and opioid-induced antinociception were studied in male Fischer 344 rats. Oxidative stress markers in cerebral cortex, hippocampus, striatum and midbrain of these rats were estimated. It was concluded that sensitivity to nociceptive stimulus increases and responses to opioids decrease with aging and age-related oxidative damage is negatively correlated with opioid-induced antinociception. To characterize the effects of oxidative stress on function of opioid receptors, changes in intracellular cyclic adenosine monophosphate (cAMP) was measured in human SK-N-SH neuronal cells under oxidative stress conditions. It was found that oxidative stress decreased the function of mu opioid receptor (MOR) but not that of delta or kappa opioid receptors (DOR and KOR respectively). Antioxidant intervention preserved the function of MOR. Western immunoassays revealed that MOR but not DOR and KOR proteins were decreased under oxidative stress conditions. Thus, these findings show a selective impairment of the MOR function and reduction in MOR protein under conditions of oxidative stress. The results from the in vivo and in vitro projects demonstrate the involvement of aging and oxidative stress in modulation of pass sensitivity, opioid-induced antinociception and opioid receptor function and expression.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/29430
dc.language.isoen
dc.provenance.legacyDownloads0
dc.subjectLife Sciences
dc.subjectMedical Neurobiology
dc.subjectMedical Pharmacology
dc.subjectMedicine and Health Sciences
dc.subjectNervous System
dc.subjectNeuroscience and Neurobiology
dc.subjectOther Neuroscience and Neurobiology
dc.subjectPharmacology
dc.subjectOpioid receptors
dc.subjectaging
dc.subjectoxidative stress
dc.subjectneurodegenerative disorders
dc.subjectin vitro
dc.subjectpain sensitivity
dc.subjectantinocicepetoin
dc.subjectdelta opioid receptor
dc.subjectkappa opioid receptor
dc.subjectmale Fischer 344 rats
dc.titleOpioid Receptors in Aging and Oxidative Stress
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplinePharmacology and Neuroscience
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
Raut_OpioidReceptorsInAging.pdf
Size:
53.78 MB
Format:
Adobe Portable Document Format
Download

Collections

School of Biomedical Sciences
Theses and Dissertations