CHRONIC L-DEPRENYL OR L-AMPHETAMINE - EQUAL COGNITIVE ENHANCEMENT, UNEQUAL MAO INHIBITION

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 acquisitio n of a learned spatial habit in a modified Morris Water Maze was inves tigated in middle aged rats. Injections, given three times weekly star ting at 6 months of age, were continued during behavioral testing, whi ch occurred at 10 months of age. The cognitive performance of the midd le aged rats was compared to that of 2-month-old control rats. Twenty- four hours after the last behavioral test, the rats were sacrificed an d their brains were removed, dissected, and frozen in liquid nitrogen. The activities of MAO-A and MAO-B in the lateral cortex were determin ed. Results indicate that rats in the L-deprenyl group, the L-amphetam ine group, and the young control group all learned the water maze task equally rapidly and significantly faster than rats in the saline grou p. MAO-A did not differ among the saline, amphetamine, and young contr ol 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 al so inhibit MAO-A following chronic SC administration. Moreover, the im proved 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. It remains to be determined whether this mechanism is produced by, shared with, or independent from depren yl's amphetamine metabolites.