1. ¹Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
2. ²Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

Correspondence: Dr A Kuzmin, Department of Clinical Neuroscience, Section of Drug Dependence Research, L4:00 Karolinska University Hospital, Stockholm S-171 76, Sweden, Tel: +46 8 51770542; Fax: +46 8 51775231; E-mail: alexander.kuzmin@neuro.ki.se

Received 8 February 2005; Revised 6 October 2005; Accepted 7 October 2005; Published online 16 November 2005.

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 -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 -opioid receptors.