D-Cycloserine and performance under different states of anxiety in healthy volunteers

There is interest in the development of augmentation therapy in the treatment of anxiety disorders. Recent publications have shown that D-cycloserine can benefit exposure therapy in a group of acrophobic (height phobic) subjects and in patients with social anxiety disorder. These studies were based on the animal data suggesting that drugs acting to enhance glutamate function may be developed to accelerate the behavioural treatment of anxiety disorders. Perhaps by enhancing glutamate/N-methyl-D-aspartate receptor function, learning is thus enhanced. This study examines the effects of D-cycloserine 50 mg on a task that involves learning. We manipulated anxiety levels to model the effects of high anxiety.

To evaluate performance and learning, we used the Manikin task. Two groups of 24 healthy volunteers participated in a double-blind, placebo-controlled study. One group received the inhalation of CO(2) 7.5% to model high anxiety, and the second group received air to represent lower anxiety. Subjects received D-cycloserine 50 mg or placebo, and the Manikin task was performed during the gas inhalation.

There were significant differences in the group inhaling air, but not CO(2), with the D-cycloserine group showing an increase in correct responses. This difference was apparent at several time blocks during the 20-min task. These findings were supported by subjective measures in that participants who received D-cycloserine reported that the task was easier.

We have shown that at lower anxiety levels, D-cycloserine 50 mg improved the performance of this challenging visuospatial cognitive task. This increase in performance was not seen when anxiety was higher, and D-cycloserine did not appear to increase subjective anxiety. These data lend support to the use of D-cycloserine and related glutamate enhancers as cognitive modulators and suggest that the actions of D-cycloserine are not simply related to increased arousal or anxiety.