The present study tested the prediction that D-cycloserine (DCS), a partial N-methyl-D-aspartate agonist, would facilitate extinction of conditioned freezing in male Sprague-Dawley rats. Rats received 5 light-shock pairings (conditioning). The following day, rats received 6 light-alone presentations (extinction training). Twenty-four hours later, rats received 1 light-alone presentation (test). Subcutaneous DCS injection before or after extinction training significantly enhanced extinction, and the dose-response curve for this effect was linear. Increasing the delay of DCS administration after extinction training led to a linear decrease in the facilitatory effect. The effect of systemic administration was replicated by intra-basolateral amygdala infusion. These results suggest that DCS facilitates extinction of conditioned freezing by acting on consolidation processes partly mediated by the basolateral amygdala.

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Several recent studies have reported that D-cycloserine (DCS), a partial N-methyl-D-aspartate agonist, facilitates extinction of learned fear in rats. Other studies have shown that representation of the unconditioned stimulus (US) can reinstate learned fear after extinction. This study examined whether this reinstatement effect occurs in Sprague-Dawley rats given DCS at the time of extinction. Results showed that saline-treated rats exhibited the reinstatement effect but DCS-treated rats did not (Experiments 1 and 2). This lack of reinstatement in DCS-treated rats was not due to residual effects of DCS on either US or context processing (Experiment 3). Overall, these results (a) raise questions about the mechanisms underlying DCS facilitation of extinction and (b) suggest that DCS might have substantial practical benefit.

Anxiety disorders are among the most common psychological disturbances in the industrialized world. Current behavioral therapy procedures for these disorders are somewhat effective, but their efficacy could be substantially improved. Because these procedures are largely based on the process of extinction, manipulations that enhance extinction may lead to improvements in treatment effectiveness. We review the evidence that D-cycloserine (DCS), a partial NMDA agonist, facilitates extinction of learned fear in rats. Although only a few studies have examined the effects of DCS on extinction of learned fear, this work suggests that this drug may have a number of potential clinical benefits. In addition, attempts at interpreting this research illustrate our limited understanding of the processes involved in extinction.A substantial percentage of the industrialized world's population will suffer from an anxiety disorder at some point, and consequently, the burden-of-disease costs (both financial and personal) associated with these disorders are extremely high (e.g., Andrews et al. 2001). As a result, there is considerable interest in developing effective treatments for anxiety disorders. Many current therapies for anxiety disorders (e.g., systematic desensitization, flooding, and implosion) involve controlled exposures to the feared stimulus. In other words, these therapies are based on the process of extinction. Although these therapies are the most effective current form of treatment for anxiety disorders (Foa 2000), they could be improved in a number of ways. For example, some patients who begin treatment fail to complete it (i.e., they drop out after a few sessions), and some patients who successfully complete treatment later relapse (i.e., their symptoms return). Manipulations that enhance the process of extinction might reasonably be expected to lead to an improved efficacy of these therapies. Specifically, if such manipulations reduce the number of sessions required, then fewer patients may fail to complete treatment. If these manipulations also somehow reduced the incidence of relapse, then their benefits would be even greater.In the past decade, considerable effort has been directed at increasing our understanding of extinction. Much of this research has involved Pavlovian conditioned fear. In such studies, an animal is first exposed to pairings of an initially neutral conditioned stimulus (CS; e.g., light or tone) with a naturally aversive unconditioned stimulus (US; e.g., shock). After this experience, presentations of the CS elicit a number of behaviors usually associated with the state of fear (e.g., tachycardia, elevated blood pressure, potentiated startle response). These learned fear responses can be reduced, however, by repeatedly presenting the CS by itself; in other words the learned fear responses can be extinguished (see Myers and Davis 2002, for operational and conceptual definitions of extinction). Although extinction is a very simple process procedurally, it has proven to be quite complex theore...