Post-retrieval oxytocin facilitates next day extinction of threat memory in humans

Abstract

Rationale. Memories can return to a labile state and become amenable to modification by pharmacological and behavioral manipulations after retrieval. This process may reduce the impact of aversive memories and provide a promising therapeutic technique for the treatment of anxiety disorders. A growing body of evidence suggests that the mammalian neuropeptide oxytocin (OT) plays a role in the regulation of emotional memories in animals. However, the effects of OT on threat memory in humans remain largely unknown. Objectives. This study aimed to investigate the effects of OT administration following threat memory retrieval on subsequent memory expression in human participants. Methods. In a double blind, randomized, placebo-controlled, between-subject design, 61 healthy human individuals completed a three-day experiment. All participants underwent threat conditioning on day 1. On day 2, participants were randomized to receive an intranasal dose of OT (40 IU) or placebo after memory retrieval, or an intranasal dose of OT (40 IU) without retrieval. On day 3, subjects were tested for extinction and reinstatement. Results. On day 3, all groups showed equivalent stimulus discrimination during the early phase of extinction. However, the group that received OT following a memory reminder showed a greater decline of stimulus discrimination by the late phase of extinction relative to the two other groups. Conclusions. The results indicate that OT did not block reconsolidation to prevent the return of threat memory but rather interacted with post-retrieval processes to facilitate next day extinction. The study provides novel preliminary evidence for the role of OT in human threat memory.

Emotional remodeling with oxytocin durably rescues trauma-induced behavioral and neuro-morphological changes in rats: a promising treatment for PTSD

“…Another possibility is that oxytocin accelerated extinction of reactivity to trauma-associated, as the result of their repeated presentations. Although oxytocin has been shown to facilitate next day extinction of threat memory in humans 63 , its role in long-term stabilization of extinction implicitly suggests that it should mediate exceptionally robust extinction process to prevent the reinstatement of fear after remote exposure to the entire set of retrieval cues. Indeed, oxytocin possesses intrinsic pharmacological properties, which are suitable to tackle maladaptive fear.…”

Editorial: the psychopharmacology of extinction—from theory to therapy

“…It is important in this regard to be open to the possibility, and then to test for, that pharmacological agents may be targeting either reconsolidation or extinction mechanisms. In an illustration of this, Schiller and colleagues (Hu et al 2019) report how oxytocin administered following re-exposure to a fear-associated cue enhanced subsequent extinction learning but without disrupting reconsolidation of the original fear memory.…”

Oxytocin and Fear Memory Extinction: Possible Implications for the Therapy of Fear Disorders?

“…On day 3, the participants were tested for extinction (image presentation without shock) and reinstatement (unsignaled mild shock without picture presentation). Despite an initial equivalent stimulus discrimination, the OXT retrieval group showed a reduction in stimulus discrimination on the late extinction phase, suggesting that OXT interacts with postretrieval processes rather that blocking consolidation to facilitate extinction [ 219 ].…”