Mesencephalic morphine antinociception: Antagonism by serotonergic and opioid antagonists in the rostral ventral medulla in rats.
Item
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Title
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Mesencephalic morphine antinociception: Antagonism by serotonergic and opioid antagonists in the rostral ventral medulla in rats.
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Identifier
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AAI9432347
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identifier
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9432347
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Creator
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Kiefel, Jacqueline Marie.
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Contributor
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Adviser: Richard J. Bodnar
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Date
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1994
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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, Physiological | Psychology, Psychobiology
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Abstract
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Supraspinal opioid antinociception is mediated in part by connections between the midbrain periaqueductal gray (PAG) and the rostral ventral medulla (RVM), which includes the nuclei raphe magnus and reticularis gigantocellularis. Little is known about the nature of the neurochemical link between the PAG and the RVM. Since both serotonergic and enkephalinergic pathways project from the PAG to the RVM, and given the existence of multiple serotonin and opioid receptor subtypes localized in the RVM, the aims of this dissertation were to evaluate the effects of intracerebral microinjections of general and specific serotonin and opioid receptor antagonists into the RVM upon morphine antinociception elicited from the PAG.;Microinjections of morphine (2.5 {dollar}\mu{dollar}g) into the PAG produced a significant antinociception on the tail-flick and jump tests. This antinociception was significantly reduced following RVM microinjections of the general serotonergic antagonist methysergide (0.5-5 {dollar}\mu{dollar}g) on the tail-flick (69%) and jump (50%) tests. To ascertain which serotonergic receptors might be responsible for the above inhibition of morphine's effects, the 5-HT{dollar}\sb2{dollar} antagonist, ritanserin (0.25-2.5 {dollar}\mu{dollar}g) and the 5-HT{dollar}\sb3{dollar} antagonist, ICS 205930 (0.25-5 {dollar}\mu{dollar}g) were microinjected into the RVM prior to microinjections of morphine into the PAG. Mesencephalic morphine antinociception was significantly reduced following pretreatment with both ritanserin on the tail-flick (81%) and jump (65%) tests and ICS 205930 on the tail-flick (91%) and jump (63%) tests.;Mesencephalic morphine antinociception was similarly reduced following pretreatment in the RVM with the general opioid receptor antagonist, naltrexone (1-10 {dollar}\mu{dollar}g) on the tail-flick (93%) and jump (89%) tests. Mesencephalic morphine antinociception was also significantly reduced by both the mu-selective antagonist, beta-funaltrexamine (0.5-5 {dollar}\mu{dollar}g) on the tail-flick (93%) and jump (91%) tests, and the delta{dollar}\sb2{dollar}-selective antagonist, naltrindole (0.5-5 {dollar}\mu{dollar}g) on the tail-flick (80%) and jump (85%) tests.;In contrast, none of the antagonists were effective in reducing mesencephalic morphine antinociception when they were microinjected into placements lateral or dorsal to the RVM. Further, none of these antagonists produced meaningful changes in basal nociceptive thresholds. These data indicate that ventro-medial medullary serotonergic receptors, specifically the 5-HT{dollar}\sb2{dollar} and 5-HT{dollar}\sb3{dollar} receptor subtypes and medullary mu and delta opioid receptors modulate the transmission of opioid pain-inhibitory signals from the PAG.
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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.
