d-CYCLOSERINE FOR TREATING ANXIETY DISORDERS: MAKING GOOD EXPOSURES BETTER AND BAD EXPOSURES WORSE
Abstract
In an attempt to improve the efficacy of psychotherapy for anxiety disorders, preclinical paradigms have recent been translated into novel treatment strategies.[1] Specifically, these studies have examined the role of glutamate, an excitatory neurotransmitter in the mammalian brain, in extinction learning. A receptor complex involved in this process is the N-methyl-D-aspartate (NMDA) receptor. Activation of the NMDA receptor requires binding of both glutamate and the co-agonist glycine. D-cycloserine (D-4-amino-3-isoxazolidone; DCS) is a partial agonist at the glycine recognition site of the glutamatergic NMDA receptor. Animal studies that employed fear-potentiated startle to a conditioned stimulus have demonstrated that this substance can augment extinction learning in rats.[1] The result of this translational work has shown for some studies that DCS can act as a cognitive enhancer to augment exposure strategies during cognitive-behavioral therapy of anxiety disorders.[2] This line of research has gathered a significant amount of attention because it is a prime example of translational research, whereby basic neuroscience directly informs clinical science by identifying a compound and mechanism of treatment change. Following the initial excitement surrounding early DCS augmentation trials, a number of studies have been conducted that provide a more refined picture. These studies further have clarified some of the limitations and indications of DCS as an augmentation strategy.