Human Perceptual Learning is Delayed by the N-methyl-D-aspartate Receptor Partial Agonist D-cycloserine

Background: The optimisation of learning has long been a focus of scientific research, particularly in relation to improving psychological treatment and recovery of brain function. Previously, partial N-methyl-D-aspartate agonists have been shown to augment reward learning, procedural learning and psychological therapy, but many studies also report no impact of these compounds on the same processes.

Aims: Here we investigate whether administration of an N-methyl-D-aspartate partial agonist (D-cycloserine) modulates a previously unexplored process - tactile perceptual learning. Further, we use a longitudinal design to investigate whether N-methyl-D-aspartate-related learning effects vary with time, thereby providing a potentially simple explanation for apparent mixed effects in previous research.

Methods: Thirty-four volunteers were randomised to receive one dose of 250 mg D-cycloserine or placebo 2 h before tactile sensitivity training. Tactile perception was measured using psychophysical methods before and after training, and 24/48 h later.

Results: The placebo group showed immediate within-day tactile perception gains, but no further improvements between-days. In contrast, tactile perception remained at baseline on day one in the D-cycloserine group (no within-day learning), but showed significant overnight gains on day two. Both groups were equivalent in tactile perception by the final testing - indicating N-methyl-D-aspartate effects changed the timing, but not the overall amount of tactile learning.

Conclusions: In sum, we provide first evidence for modulation of perceptual learning by administration of a partial N-methyl-D-aspartate agonist. Resolving how the effects of such compounds become apparent over time will assist the optimisation of testing schedules, and may help resolve discrepancies across the learning and cognition domains.