Supraspinal opiate antinociception: Synergy between mesencephalic, pontine and medullary sites in the rat.
Item
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Title
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Supraspinal opiate antinociception: Synergy between mesencephalic, pontine and medullary sites in the rat.
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Identifier
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AAI9405582
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identifier
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9405582
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Creator
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Rossi, Grace C.
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Contributor
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Mentor: Richard J. Bodnar
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Date
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1993
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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 | Psychology, Behavioral | Biology, Neuroscience
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Abstract
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Morphine produces potent antinociception when injected into the periaqueductal gray (PAG), the rostral ventral medulla (RVM: nuclei raphe magnus and reticularis gigantocellularis), and the dorsolateral pons (DLP) which includes the locus coeruleus. Supraspinal opioid antinociception is mediated by intrinsic connections among these structures. Simultaneous administration of sub-antinociceptive doses of morphine into pairs of these three sites elicited dramatic antinociception, implying synergy. The most effective combination was the PAG and RVM; the PAG/DLP and RVM/DLP combinations were less efficacious. The marked synergy between the PAG and the RVM was sensitive to naloxonazine, implying a role for mu{dollar}\sb1{dollar} receptors. Inclusion of a low morphine dose in one region produced significant leftward shifts in the other's antinociceptive dose response curve.;This dissertation then characterized the opioid receptor subtypes involved in the multiplicative antinociceptive interaction between the PAG and RVM through the use of agonists of mu (D-Ala{dollar}\sp2{dollar}, Met-Phe{dollar}\sp4{dollar}, Gly(ol){dollar}\sp5{dollar}-enkephalin: DAMGO), kappa (U50488H), delta{dollar}\sb1{dollar} (D-Pen{dollar}\sp2{dollar}, D-Pen{dollar}\sp5{dollar}- enkephalin: DPDPE) and delta{dollar}\sb2{dollar} (deltorphin II) receptors. DAMGO (1-20 ng) dose-dependently increased tail-flick latencies in the PAG and RVM, and sub-antinociceptive doses of DAMGO administered simultaneously to the two sites produced strong multiplicative interactions. In contrast, neither U50,488H (20 {dollar}\mu{dollar}g) nor DPDPE (20 {dollar}\mu{dollar}g) altered latencies in the PAG and RVM, and failed to produce any interactive effects when paired with DAMGO. Deltorphin (20 {dollar}\mu{dollar}g) produced a mild antinociception in the PAG and RVM, and its simultaneous administration to the two sites produced small interactive effects. Simultaneous administration of deltorphin (10 {dollar}\mu{dollar}g)and DAMGO (3 ng) to the two sites produced a profound multiplicative interaction. In contrast, deltorphin and DPDPE failed to produce interactive effects. These data indicate that antinociceptive opioid synergy occurs between the PAG, RVM and DLP with the most pronounced effects in the PAG and RVM mediated by mu{dollar}\sb1{dollar}, and to a lesser degree, delta{dollar}\sb2{dollar}, opioid receptors.
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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.
