The NMDA receptor partial agonist d-cycloserine does not enhance motor learning

Abstract

Rationale: There has recently been increasing interest in pharmacological manipulations that could potentially enhance exposure-based cognitive behaviour therapy for anxiety disorders. One such medication is the partial NMDA agonist d-cycloserine. It has been suggested that d-cycloserine enhances cognitive behaviour therapy by making learning faster. While animal studies have supported this view of the drug accelerating learning, evidence in human studies has been mixed. We therefore designed an experiment to measure the effects of d-cycloserine on human motor learning.

Methods: Fifty-four healthy human volunteers were randomly assigned to a single dose of 250mg d-cycloserine versus placebo in a double-blind design. They then performed a motor sequence learning task.

Results: D-cycloserine did not increase the speed of motor learning or the overall amount learnt. However, we noted that participants on d-cycloserine tended to respond more carefully (shifting towards slower, but more correct responses).

Conclusion: The results suggest that d-cycloserine does not exert beneficial effects on psychological treatments via mechanisms involved in motor learning. Further studies are needed to clarify the influence on other cognitive mechanisms.

Keywords: NMDA; d-cycloserine; motor learning.

Figure 1.

Behavioural results. (a) Plot of the log-transformed reaction times across the learning and the two consolidation phases for the d-cycloserine (circles) and the placebo (triangles, dashed line) groups. The initial learning blocks were the 15 sequence learning blocks (blocks 2 to 14, 16 and 17) while participants performed a random sequence in blocks 1 and 15. Each consolidation phase consisted of three sequence blocks. There were no group differences in either the initial learning or the consolidation (all p>0.9). (b) Balance scores (i.e. log-transformed reaction times multiplied by accuracy) across the learning task and consolidation. Error bars show the standard error of the mean, *p<0.055.