Single-dose hydrocortisone administration does not enhance motor sequence learning or reward learning in humans.

Despite its physiological and clinical relevance, the influence of hydrocortisone on specific kinds of learning remains relatively unexplored. We measured the effect of hydrocortisone on motor sequence and reward learning under non-stress conditions. For the study, 54 healthy young volunteers were randomly assigned to a dose of 20 mg hydrocortisone versus placebo. Participants performed two well-defined learning tasks. Hydrocortisone did not affect motor sequence or reward learning.

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

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.

A role beyond learning for NMDA receptors in reward-based decision-making-a pharmacological study using d-cycloserine.

N-methyl-D-aspartate (NMDA) receptors are known to fulfill crucial functions in many forms of learning and plasticity. More recently, biophysical models, however, have suggested an additional role of NMDA receptors in evidence integration for decision-making, going beyond their role in learning. We designed a task to study the role of NMDA receptors in human reward-guided learning and decision-making. Human participants were assigned to receive either 250 mg of the partial NMDA agonist d-cycloserine (n=20) or matching placebo capsules (n=27). Reward-guided learning and decision-making were assessed using a task in which participants had to integrate learnt and explicitly shown value information to maximize their monetary wins and minimize their losses. To tease apart the effects of NMDA on learning and decision-making we used simple learning models. D-cycloserine shifted decision-making towards a more optimal integration of the learnt and the explicitly shown information, in the absence of a direct learning effect. In conclusion, our results reveal a distinct role for NMDA receptors in reward-guided decision-making. We discuss these findings in the context of NMDA's roles in neuronal super-additivity and as crucial for evidence integration for decisions.