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.

Decades of behavioral studies have confirmed that extinction does not erase classically conditioned fear memories. For this reason, research efforts have focused on the mechanisms underlying the development of extinction-induced inhibition within fear circuits. However, recent studies in rodents have uncovered mechanisms that stabilize and destabilize fear memories, opening the possibility that extinction might be used to erase fear memories. This symposium focuses on several of these new developments, which involve the timing of extinction training. Extinction-induced erasure of fear occurs in very young rats, but is lost with the development of perineuronal nets in the amygdala that render fear memories impervious to extinction. Moreover, extinction administered during the reconsolidation phase, when fear memory is destabilized, updates the fear association as safe, thereby preventing the return of fear, in both rats and humans. The use of modified extinction protocols to eliminate fear memories complements existing pharmacological strategies for strengthening extinction.