CHRONIC ADMINISTRATION OF NEUROKININ SP IMPROVES MAZE PERFORMANCE IN AGED RATTUS-NORVEGICUS

Deficits in associative functions seen with senescence may be based, at least in part, on a decreased availability of trophic factors in the CNS. A reduced concentration of neurokinins, including undecapeptide substance P (SP), also accompanies aging. Thus, given the change in SP metabolism and the known mnemogenic as well as neurotrophic/neuroprotective effects of the peptide, it seems possible that age-related deficits in associative processes could be influenced by treatment with exogenous SP. In the present study, 30-month-old Wistar rats were injected daily with SP (50 or 250 mu g/kg, intraperitoneally) starting 1 week before they were tested on the Morris water maze task and on motor coordination tests. Control groups included vehicle-injected old and adult (3-month-old) rats. Over the days of maze testing, application of the substances was performed 5 h after testing daily for 15 days and after the last drug delivery, maze testing was continued for 4 more days. The main finding of this study is that chronic administration of both dosages of SP (50 and 250 mu g/kg) improved the maze performance of the old rats. This facilitatory effect of SP on performance was also evident after the drug treatment had been terminated in the course of maze testing. Furthermore, chronic application of SP in a dose range of 50-250 mu g/kg was found to reduce age-related deficits in motor capacities. (C) 1994 Academic Press, Inc.