Dynorphin-A-(1-13) antagonizes morphine analgesia in the brain and potentiates morphine analgesia in the spinal cord

Peptides. Nov-Dec 1985;6(6):1015-20. doi: 10.1016/0196-9781(85)90423-1.

Abstract

Intrathecal injection of subanalgesic doses of morphine (7.5 nmol) and dynorphin-A-(1-13) (1.25 nmol) in combination resulted in a marked analgesic effect as assessed by tail flick latency in the rat. The analgesic effect of the composite dynorphin/morphine was dose-dependent in serial dilutions so that a composition of 1/8 of the analgesic dose of dynorphin and 1/3 that of morphine produced an analgesic effect equipotent to full dose of either drug applied separately. The analgesic effect induced by dynorphin/morphine mixture was not accompanied by motor dysfunction and was easily reversed by a small dose (0.5 mg/kg) of naloxone. Contrary to the augmentatory effect of dynorphin on morphine analgesia in the spinal cord, intracerevroventricular (ICV) injection of 20 nmol of dynorphin-A-(1-13) exhibited a marked antagonistic effect on the analgesia produced by morphine (120 nmol, ICV). The theoretical considerations and practical implications of the differential interactions between dynorphin-A-(1-13) and morphine in the brain versus spinal cord are discussed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesia
  • Animals
  • Brain / drug effects
  • Brain / physiology*
  • Cerebral Ventricles / physiology
  • Drug Synergism
  • Dynorphins / administration & dosage
  • Dynorphins / pharmacology*
  • Female
  • Injections, Intraventricular
  • Morphine / antagonists & inhibitors
  • Morphine / pharmacology*
  • Naloxone / pharmacology
  • Narcotics / pharmacology*
  • Organ Specificity
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology*
  • Rats
  • Spinal Cord / drug effects
  • Spinal Cord / physiology*

Substances

  • Narcotics
  • Peptide Fragments
  • Naloxone
  • dynorphin (1-13)
  • Dynorphins
  • Morphine