D-Serine has also been tested in preclinical models of cognition. D-Cycloserine has been extensively tested as an adjunct to cognitive remediation, but D-serine, as a full agonist, is hypothesized to be more effective at enhancing NMDA function and cognitive remediation. This hypothesis was supported by a preclinical study [43▪] in which D-serine enhanced recognition and working memory in mice. These improvements were associated with measurable increases in hippocampal D-serine. Additionally, D-serine reversed the effects of an NMDA antagonist. Of particular interest, this was the first preclinical demonstration of clinically relevant doses (50 vs. >600 mg/kg) being effective, and, moreover, demonstrated that, as opposed to D-cycloserine, D-serine may have continued effectiveness during repeated administration.
