Different Effects of Scopolamine and Inhibition of Prolyl Oligopeptidase on Mnemonic and Motility Functions of Young and 8- to 9-Month-Old Rats in the Radial-Arm Maze

Abstract: Prolyl oligopeptidase (POP) has been connected to memory and mood through regulation of the brain levels of its biologically active peptide substrates and phosphatidylinositol system. This is the first study in a radial-arm maze of the effects of a single dose of a novel potent prolyl oligopeptidase inhibitor, KYP-2047 (5 mg/kg, dissolved in 5% Tween 80), on memory and learning of scopolamine-treated (0.4 mg/kg, dissolved in saline) rats. Habituated (days 1 and 2) and trained (days 3–11) young (3 months) and old (8–9 months) male Wistar rats were given (i) saline + Tween, (ii) saline + KYP-2047, (iii) scopolamine + Tween or (iv) scopolamine + KYP-2047 30 min. prior to testing their memory. Food rewards located in four randomly chosen arms of the maze. The rat had 10 min. to find and eat the rewards. Time spent in the maze, visits to each arm and number of eaten rewards were measured. Old rats made generally more errors, spent more time and visited fewer arms per minute in the maze than young rats. The memory- and function-impairing effects of scopolamine were also seen more clearly in old than young rats. KYP-2047 had no or only a marginal effect on memory of either age group, but when given without scopolamine, it slightly increased the maze motility of young rats and decreased the motility of old rats. In a separate locomotor activity test, KYP-2047 enhanced the motility of young rats supporting a suggested role of POP in motor functions.