Central alloxan and opioid and nonopioid antinociception in rats: Differential effects and specificity of action.
Item
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Title
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Central alloxan and opioid and nonopioid antinociception in rats: Differential effects and specificity of action.
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Identifier
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AAI9119651
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identifier
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9119651
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Creator
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Lubin, Edward.
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Contributor
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Adviser: Richard J. Bodnar
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Date
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1991
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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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Biology, Neuroscience | Psychology, Psychobiology | Psychology, Physiological
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Abstract
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2-Deoxy-D-glucose (2DG) antinociception, mediated in part by endogenous opiate and hypothalamo-hypophysial systems, is presumably activated by its stress-related properties. 2DG hyperphagia, but not 2DG hyperglycemia, is reduced by central pretreatment with alloxan. While peripheral alloxan potently produces pancreatic beta-cell toxicity, much lower intracerebroventricular (ICV) doses reduce glucoprivic feeding in the absence of hypoglycemia. This deficit is eliminated by coadministration of 3M D-glucose. Our first experiment examined whether ICV pretreatment with alloxan at two doses (40 and 200 {dollar}\mu{dollar}g) alters 2DG antinociception (400 and 700 mg/kg, IP) on the tail-flick and jump tests in rats, and whether 3M D-glucose coadministration ameliorates any deficits. Alloxan significantly reduces 2DG antinociception in a dose-dependent manner. 3M D-glucose coadministration ameliorates alloxan-induced antinociceptive deficits more effectively at the lower 2DG dose. Neither alloxan nor alloxan/3M D-glucose treatments altered basal thresholds. These data pertain both to alloxan's effects upon coding of 2DG effects as stressful, and to the role of central glucoreceptors in antinociceptive processes.;We examined ICV and intravenous (IV) alloxan (200 {dollar}\mu{dollar}g) on morphine antinociception (1-10 mg/kg, SC) as well as ICV alloxan upon nonopioid-mediated continuous cold-water swim (CCWS: 2{dollar}\sp\circ{dollar}C for 3.5 min) and antinociception following the muscarinic receptor agonist, pilocarpine (0.5, 2 and 5 mg/kg, IP). Morphine (2.5 and 5.0 mg/kg, SC) antinociception was markedly reduced on both tail-flick and jump tests two weeks following central, but not peripheral, pretreatment with alloxan. In contrast, central pretreatment with alloxan had mixed effects upon CCWS antinociception. Finally, alloxan generally failed to alter nonopioid pilocarpine antinociception. These effects occurred in the absence of changes in basal nociceptive thresholds, hypothermia or hypoglycemia.;We then examined the effects of alloxan and structurally similar compounds, allantoin and uracil, possessing no diabetogenic activity, on morphine antinociception. Whereas alloxan significantly reduces morphine antinociception across the dose and time course, regression analysis to determine potency effects shows that uracil and allantoin are generally incapable of reducing morphine antinociception. These data suggest a functional and structural specificity of alloxan in inducing the effects seen in opioid function.
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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.
