Delta/mu opioid receptor interactions in operant conditioning assays of pain-depressed responding and drug-induced rate suppression: assessment of therapeutic index in male Sprague Dawley rats.

Rationale and objectives: Although delta/mu receptor interactions vary as a function of behavioral endpoint, there have been no assessments of these interactions using assays of pain-depressed responding. This is the first report of delta/mu interactions using an assay of pain-depressed behavior.Met...

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Publicado en:Psychopharmacology Vol. 235; no. 5; pp. 1609 - 1619
Autores principales: Cone, Katherine, Lanpher, Janell, Kinens, Abigail, Richard, Philomena, Couture, Sarah, Brackin, Rebecca, Payne, Emily, Harrington, Kylee, Rice, Kenner C., Stevenson, Glenn W.
Formato: Journal Article
Publicado: Springer Nature May2018
Acceso en línea:Ver este registro en EBSCOhost
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      place: New York, New York
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        10.1007/s00213-018-4876-x
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        atl: Delta/mu opioid receptor interactions in operant conditioning assays of pain-depressed responding and drug-induced rate suppression: assessment of therapeutic index in male Sprague Dawley rats.
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        au:
          Cone, Katherine
          Lanpher, Janell
          Kinens, Abigail
          Richard, Philomena
          Couture, Sarah
          Brackin, Rebecca
          Payne, Emily
          Harrington, Kylee
          Rice, Kenner C.
          Stevenson, Glenn W.
        affil: Department of Psychology, University of New England, 04005, Biddeford, ME, USA
      sug:
      ab: Rationale and objectives: Although delta/mu receptor interactions vary as a function of behavioral endpoint, there have been no assessments of these interactions using assays of pain-depressed responding. This is the first report of delta/mu interactions using an assay of pain-depressed behavior.Methods: A mult-cycle FR10 operant schedule was utilized in the presence of (nociception) and in the absence of (rate suppression) a lactic acid inflammatory pain-like manipulation. SNC80 and methadone were used as selective/high efficacy delta and mu agonists, respectively. Both SNC80 and methadone alone produced a dose-dependent restoration of pain-depressed responding and dose-dependent response rate suppression. Three fixed ratio mixtures, based on the relative potencies of the drugs in the nociception assay, also produced dose-dependent antinociception and sedation. Isobolographic analysis indicated that all three mixtures produced supra-additive antinociceptive effects and simply additive sedation effects.Conclusions: The therapeutic index (TI) inversely varied as a function of amount of SNC80 in the mixture, such that lower amounts of SNC80 produced a higher TI, and larger amounts produced a lower TI. Compared to literature using standard pain-elicited assays, the orderly relationship between SNC80 and TI reported here may be a unique function of assessing pain-depressed behavior.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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