Big dynorphin, a prodynorphin-derived peptide produces NMDA receptor-mediated effects on memory, anxiolytic-like and locomotor behavior in mice.
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.
Kuzmin
Alexander
A
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. alexander.kuzmin@neuro.ki.se
Madjid
Nather
N
Terenius
Lars
L
Ogren
Sven Ove
SO
Bakalkin
Georgy
G
D000595:Amino Acid Sequence; D000818:Animals; D014151:Anti-Anxiety Agents; D001007:Anxiety / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000494:pharmacology*; D004745:Enkephalins / Q000494:pharmacology*; D006358:Hot Temperature; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D011498:Protein Precursors / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D004745:Enkephalins; D011498:Protein Precursors; D016194:Receptors, N-Methyl-D-Aspartate; C051844:norbinaltorphimine; D009271:Naltrexone; D004399:Dynorphins; C033660:preproenkephalin