Increasing evidence indicates that acute stress disrupts cognitive functions mediated by glutamate- NMDA receptors, although the mechanisms are not fully understood. Here we investigated whether Dserine and glycine, the endogenous co-agonists of the NMDA receptor, are regulated by acute stress. We studied the biochemical and behavioral effects of acute restraint stress in C57BL/6 mice. Acute restraint stress decreased D-serine levels in the prefrontal cortex and glycine levels in the hippocampus. Behaviorally, acute stress impaired memory consolidation in the object recognition task and prepulse inhibition of the startle response. Importantly, D-serine administration (1 g/kg, i.p.) prevented both stressinduced impairments. Taken together, our results show for the first time an interplay between stress and D-serine and warrant further research on the role of D-serine in stress-related disorders.