Persistent Link:
http://hdl.handle.net/10150/184918
Title:
Antinociceptive actions of central opioid delta receptors.
Author:
Heyman, Julius Scott.
Issue Date:
1989
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Opioids produce myriad effects, perhaps the most clinically relevant of which is the relief of pain. The understanding of the functions mediated by opioid systems is complicated greatly by the presence of several opioid receptor types. Understanding the functions associated with specific opioid receptors may lead to the development of receptor selective drugs which elicit only desirable effects. This dissertation addresses the possibility that supraspinal and spinal opioid δ receptors mediate and/or modulate thermal antinociceptive processes in the mouse. A number of approaches were utilized in parallel in this investigation which included: (1) the determination of the naloxone pA₂ in vivo against the opioid agonists morphine (μ), (D-Ala², NMePhe⁴, Gly-ol]enkephalin (DAMGO)(μ) and [D-Pen², D-Pen⁵]enkephalin (DPDPE)(δ); (2) the investigation of possible cross-tolerance between morphine and DPDPE; and (3) antagonism studies using N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-Oh, (ICI 174,864)(δ), β-funaltrexamine(β-FNA)(μ) and naloxonazine (μ₁). No differences were found in the apparent pA₂ values for naloxone against morphine, DAMGO and DPDPE at either supraspinal or spinal sites, but was demonstrated in the spinal cord. The antinociceptive effects of i.c.v. morphine and DAMGO were antagonized by β-FNA and naloxonazine, but not ICI 174,864. I.c.v. DPDPE antinociception was blocked by ICI 174,864, but not β-FNA or naloxonazine. Neither ICI 174,864 nor naloxonazine blocked the antinociceptive effects of i.th. morphine or DAMGO. ICI 174,864, but not naloxonazine, antagonized i.th. DPDPE antinociception. I.th. morphine, but not i.th. DPDPE antinociception was blocked by β-FNA. Co-administration of sub-effective doses of DPDPE and DAMA were shown to potentiate and attenuate, respectively, i.c.v., morphine antinociception. This potentiation was evident in naive and morphine tolerant mice, and was blocked by ICI 174,864. The modulatory effects of DPDPE and DAMA were blocked by β-FNA, but not naloxonazine. In contrast the supraspinal sites, i.th. DPDPE had no effect upon i.th. morphine antinociception. Collectively, the data demonstrate that supraspinal and spinal opioid δ receptors can directly mediate antinociception in the mouse. Additionally, supraspinal, but not spinal, δ receptors are also capable of indirectly modulating antinociceptive.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Opioids -- Receptors.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Pharmacology and Toxicology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Porreca, Frank

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleAntinociceptive actions of central opioid delta receptors.en_US
dc.creatorHeyman, Julius Scott.en_US
dc.contributor.authorHeyman, Julius Scott.en_US
dc.date.issued1989en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractOpioids produce myriad effects, perhaps the most clinically relevant of which is the relief of pain. The understanding of the functions mediated by opioid systems is complicated greatly by the presence of several opioid receptor types. Understanding the functions associated with specific opioid receptors may lead to the development of receptor selective drugs which elicit only desirable effects. This dissertation addresses the possibility that supraspinal and spinal opioid δ receptors mediate and/or modulate thermal antinociceptive processes in the mouse. A number of approaches were utilized in parallel in this investigation which included: (1) the determination of the naloxone pA₂ in vivo against the opioid agonists morphine (μ), (D-Ala², NMePhe⁴, Gly-ol]enkephalin (DAMGO)(μ) and [D-Pen², D-Pen⁵]enkephalin (DPDPE)(δ); (2) the investigation of possible cross-tolerance between morphine and DPDPE; and (3) antagonism studies using N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-Oh, (ICI 174,864)(δ), β-funaltrexamine(β-FNA)(μ) and naloxonazine (μ₁). No differences were found in the apparent pA₂ values for naloxone against morphine, DAMGO and DPDPE at either supraspinal or spinal sites, but was demonstrated in the spinal cord. The antinociceptive effects of i.c.v. morphine and DAMGO were antagonized by β-FNA and naloxonazine, but not ICI 174,864. I.c.v. DPDPE antinociception was blocked by ICI 174,864, but not β-FNA or naloxonazine. Neither ICI 174,864 nor naloxonazine blocked the antinociceptive effects of i.th. morphine or DAMGO. ICI 174,864, but not naloxonazine, antagonized i.th. DPDPE antinociception. I.th. morphine, but not i.th. DPDPE antinociception was blocked by β-FNA. Co-administration of sub-effective doses of DPDPE and DAMA were shown to potentiate and attenuate, respectively, i.c.v., morphine antinociception. This potentiation was evident in naive and morphine tolerant mice, and was blocked by ICI 174,864. The modulatory effects of DPDPE and DAMA were blocked by β-FNA, but not naloxonazine. In contrast the supraspinal sites, i.th. DPDPE had no effect upon i.th. morphine antinociception. Collectively, the data demonstrate that supraspinal and spinal opioid δ receptors can directly mediate antinociception in the mouse. Additionally, supraspinal, but not spinal, δ receptors are also capable of indirectly modulating antinociceptive.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectOpioids -- Receptors.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmacology and Toxicologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorPorreca, Franken_US
dc.contributor.committeememberBurks, Thomas F.en_US
dc.contributor.committeememberFisher, Laurel A.en_US
dc.contributor.committeememberHalpert, James R.en_US
dc.contributor.committeememberLaird, Hugh E.en_US
dc.identifier.proquest9013175en_US
dc.identifier.oclc703440468en_US
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