The possible involvement of hippocampal N-methyl-D-aspartate (NMDA) receptors in spatial reference and working memory was investigated. Rats were first trained in a four-baited/four-unbaited version of the eight-arm radial maze task in which only predetermined four arms for each rat were baited with a Food pellet. After rats reached the learning criterion, their performance was tested under the treatment of a NMDA antagonist, AP5 (D,L-2-amino-5-phosphonopentanoic acid, 20-40 nmol), or vehicle into the dorsal hippocampus through the bilaterally implanted guide cannulae. AP5 produced dose-dependent increments on both reference and working memory errors, but did not have any effect on the running speed. Additionally, there were significant correlations between the number of trials to criterion in acquisition and the number of reference and working memory errors induced by AP5 treatment. The results suggest that hippocampal NMDA receptors are involved in both spatial reference and working memory. (C) 2015 Elsevier By. All rights reserved,