Evidence for the involvement of D-aspartic acid in learning and memory of rat

D-Aspartic acid (D-Asp) is an endogenous amino acid present in neuroendocrine systems. Here, we report evidence that D-Asp in the rat is involved in learning and memory processes. Oral administration of sodium D-aspartate (40 mM) for 12-16 days improved the rats' cognitive capability to find a hidden platform in the Morris water maze system. Two sessions per day for three consecutive days were performed in two groups of 12 rats. One group was treated with Na-D-aspartate and the other with control. A significant increase in the cognitive effect was observed in the treated group compared to controls (two-way ANOVA with repeated measurements: F(2, 105) = 57.29; P value<0.001). Five further sessions of repeated training, involving a change in platform location, also displayed a significant treatment effect [F (2, 84) = 27.62; P value<0.001]. In the hippocampus of treated rats, D-Asp increased by about 2.7-fold compared to controls (82.5 ± 10.0 vs. the 30.6 ± 5.4 ng/g tissue; P<0.0001). Moreover, 20 randomly selected rats possessing relatively high endogenous concentrations of D-Asp in the hippocampus were much faster in reaching the hidden platform, an event suggesting that their enhanced cognitive capability was functionally related to the high levels of D-Asp. The correlation coefficient calculated in the 20 rats was R = -0.916 with a df of 18; P<0.001. In conclusion, this study provides corroborating evidence that D-aspartic acid plays an important role in the modulation of learning and memory. ©Springer-Verlag 2009.