FACILITATING EFFECTS OF SR 57746A ON SHORT-TERM-MEMORY IN AN OPERANT DELAYED ALTERNATION TASK IN AGED RATS

The effects of SR 57746A during acquisition and on stabilized performance of a delayed alternation task in a Skinner Box (Model E 10.10, Coulbourn Instruments, Lehigh Valley, PA) were investigated in aged rats (22-26 months old). Test sessions consisted of repeated trials during which animals were first presented with a single lever (left or right) followed several seconds later by two levers. A press on the lever opposite to that presented previously (delayed alternation) was rewarded. The number of correct responses and the reaction times to the one- and two-lever presentations were recorded. SR 57746A (0.3 and 3 mg/kg p.o.) was first evaluated during the acquisition of the delayed alternation, given before each of in daily acquisition sessions to different groups of aged animals. The imposed delay was 5 sec. Afterward, training continued without drug until asymptotic performance was reached. Rats were then given repeated drug test sessions during which different intervals (5, 10, and 20 sec) were presented in a random order. During this phase, both young and aged animals received all the different treatments (SR 57746A at 0.3, 1, and 3 mg/kg and vehicle p.o.). Aged animals showed clear deficits during both acquisition and stabilized performance phases. SR 57746A, particularly at the highest dose tested (3 mg/kg p.o.), clearly increased response accuracy of aged animals both during acquisition of the delayed alternation and during stabilized performance. In the latter phase, the facilitation of response accuracy was observed only in conditions (10 sec retention delay) where aged animals showed a deficit compared with young animals. SR 57746A did not affect response accuracy during stabilized performance in young animals at any delay. The drug-induced increase in response accuracy in aged animals occurred at a dose of SR 57746A (3 mg/kg p.o.) that lengthened reaction times, particularly simple reaction times, during both acquisition and stabilized performance and also lengthened reaction times in young animals during the stabilized performance phase. These results suggest that SR 57746A specifically attenuates age-related short-term memory impairment in rats. (C) 1995 Wiley-Liss, Inc.