The effect of chronic (4 month), subcutaneous injections of saline, L-deprenyl (0.25 mg/kg), or L-amphetamine (0.25 mg/kg) on the acquisition of a learned spatial habit in a modified Morris Water Maze was investigated in middle aged rats. Injections, given three times weekly starting at 6 months of age, were continued during behavioral testing, which occurred at 10 months of age. The cognitive performance of the middle aged rats was compared to that of 2-month-old control rats. Twenty-four hours after the last behavioral test, the rats were sacrificed and their brains were removed, dissected, and frozen in liquid nitrogen. The activities of MAO-A and MAO-B in the lateral cortex were determined. Results indicate that rats in the L-deprenyl group, the L-amphetamine group, and the young control group all learned the water maze task equally rapidly and significantly faster than rats in the saline group. MAO-A did not differ among the saline, amphetamine, and young control rats, but MAO-B was significantly higher in the middle aged saline and L-amphetamine rats than in the young controls. Both MAO-A and MAO-B activities were significantly lower in the L-deprenyl group than in the other three groups. This indicates that low-dose L-deprenyl can also inhibit MAO-A following chronic SC administration. Moreover, the improved cognitive performance produced by L-deprenyl may not be due to its ability to inhibit MAO-B, but rather to some other effect such as the activation of growth factors.(ABSTRACT TRUNCATED AT 250 WORDS)