Effects of D-cycloserine on extinction of conditioned freezing.

Abstract

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.

Glutamate NMDA Receptors within the Amygdala Participate in the Modulatory Effect of Glucocorticoids on Extinction of Conditioned Fear in Rats

“…Recent studies indicate that glutamate NMDA receptors in the amygdala play a critical role in the extinction of conditioned fear (Walker et al, 2002;Ledgerwood et al, 2003Ledgerwood et al, , 2004Yang and Lu, 2005). This experiment assessed the role of amygdaloid NMDA receptors in the DEX effect, two glutamate NMDA receptor antagonists (7)-HA966 and MK801 were used.…”

“…These results suggest that brain glucocorticoids may be involved in the dysregulation of fear memory extinction in PTSD patients. Evidence also indicated that administration of the partial NMDA receptor agonist D-cycloserine (DCS) facilitated extinction of conditioned fear (Walker et al, 2002;Ledgerwood et al, 2003Ledgerwood et al, , 2004Ressler et al, 2004;Yang and Lu, 2005) and numerous signaling cascades are involved in the DCS effect on extinction that include mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI-3 kinase) and calcineurin (Yang and Lu, 2005). The amygdaloid NMDA receptors may be also involved in the facilitatory effect of glucocorticoids on the extinction.…”

Extract of Ginkgo biloba EGb761 Facilitates Extinction of Conditioned Fear Measured by Fear-Potentiated Startle

“…Converging evidence from a variety of studies indicates that the process of extinction can be enhanced with pharmacological intervention (Walker et al, 2002;Ledgerwood et al, 2003Ledgerwood et al, , 2004Yang et al, 2005b). Ours is the first study we know of showing that acute systemic administration of EGb761 facilitated extinction of conditioned fear.…”

“…Recently, glutamate NMDA receptor agonist DCS and glucocorticoid receptor agonist dexamethasone are documented to facilitate extinction of conditioned fear (Walker et al, 2002;Yang et al, 2005b). Either before or after extinction training, systemic injections of DCS (Ledgerwood et al, 2003; or dexamethasone (Yang et al, 2005b) facilitated extinction of conditioned fear. When EGb761 was administered immediately after extinction training, it did not show any facilitation.…”

“…Recent studies show systemic infusion of glutamate NMDA receptor agonist D-cycloserine (DCS) (Ledgerwood et al, 2003; or glucocorticoid agonist dexamethasone (DEX) (Yang et al, 2005b) after extinction training facilitate extinction. This suggests that DCS and DEX are involved in the postlearning consolidation phase of the extinction memory.…”