In healthy volunteers, the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine significantly reduced the amplitude of mismatch negativity (MMN) brain responses to pitch and duration changes by 27% and 21%, respectively. Ketamine also impaired performance on a continuous performance test, decreasing hit rates and increasing specific context-dependent errors (BX errors), indicating a failure to form and use transient memory traces. These findings suggest that NMDARs are critically involved in generating MMN and that NMDAR dysfunction may underlie deficits in transient memory at different levels of information processing in schizophrenia.
D-cycloserine (DCS) did not substitute for ketamine in ketamine-dependent rats, suggesting low abuse potential. The study used a self-administration paradigm to evaluate whether DCS would be self-administered by rats trained to self-administer ketamine. DCS failed to maintain ketamine-reinforced behavior, indicating it lacks the reinforcing properties associated with abuse liability. This finding contrasts with NMDAR antagonist antidepressants, which have known potential for abuse. The results suggest DCS may have a lower risk of addiction compared to other drugs in its class.