Big dynorphin, a prodynorphin-derived peptide produces NMDA receptor-mediated effects on memory, anxiolytic-like and locomotor behavior in mice

Neuropsychopharmacology. 2006 Sep;31(9):1928-37. doi: 10.1038/sj.npp.1300959. Epub 2005 Nov 16.

Abstract

Effects of big dynorphin (Big Dyn), a prodynorphin-derived peptide consisting of dynorphin A (Dyn A) and dynorphin B (Dyn B) on memory function, anxiety, and locomotor activity were studied in mice and compared to those of Dyn A and Dyn B. All peptides administered i.c.v. increased step-through latency in the passive avoidance test with the maximum effective doses of 2.5, 0.005, and 0.7 nmol/animal, respectively. Effects of Big Dyn were inhibited by MK 801 (0.1 mg/kg), an NMDA ion-channel blocker whereas those of dynorphins A and B were blocked by the kappa-opioid antagonist nor-binaltorphimine (6 mg/kg). Big Dyn (2.5 nmol) enhanced locomotor activity in the open field test and induced anxiolytic-like behavior both effects blocked by MK 801. No changes in locomotor activity and no signs of anxiolytic-like behavior were produced by dynorphins A and B. Big Dyn (2.5 nmol) increased time spent in the open branches of the elevated plus maze apparatus with no changes in general locomotion. Whereas dynorphins A and B (i.c.v., 0.05 and 7 nmol/animal, respectively) produced analgesia in the hot-plate test Big Dyn did not. Thus, Big Dyn differs from its fragments dynorphins A and B in its unique pattern of memory enhancing, locomotor- and anxiolytic-like effects that are sensitive to the NMDA receptor blockade. The findings suggest that Big Dyn has its own function in the brain different from those of the prodynorphin-derived peptides acting through kappa-opioid receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anti-Anxiety Agents*
  • Anxiety / psychology*
  • Behavior, Animal / drug effects*
  • Dose-Response Relationship, Drug
  • Dynorphins / pharmacology*
  • Enkephalins / pharmacology*
  • Hot Temperature
  • Male
  • Memory / drug effects*
  • Mice
  • Molecular Sequence Data
  • Motor Activity / drug effects*
  • Naltrexone / analogs & derivatives
  • Naltrexone / pharmacology
  • Pain Measurement / drug effects
  • Protein Precursors / pharmacology*
  • Reaction Time / drug effects
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / drug effects*

Substances

  • Anti-Anxiety Agents
  • Enkephalins
  • Protein Precursors
  • Receptors, N-Methyl-D-Aspartate
  • norbinaltorphimine
  • Naltrexone
  • Dynorphins
  • preproenkephalin