title: Extinction after retrieval: effects on the associative and nonassociative components of remote contextual fear memory.
abstract: Long-lasting memories of adverse experiences are essential for individuals' survival but are also involved, in the form of recurrent recollections of the traumatic experience, in the aetiology of anxiety diseases (e.g., post-traumatic stress disorder [PTSD]). Extinction-based erasure of fear memories has long been pursued as a behavioral way to treat anxiety disorders; yet, such a procedure turns out to be transient, context-dependent, and ineffective unless it is applied immediately after trauma. Recent evidence indicates that, in both rats and humans, extinction training can prevent the return of fear if administered within the reconsolidation window, when memories become temporarily labile and susceptible of being updated. Here, we show that the reconsolidation-extinction procedure fails to prevent the spontaneous recovery of a remote contextual fear memory in a mouse model of PTSD, as well as the long-lasting behavioral abnormalities induced by traumatic experience on anxiety and in both social and cognitive domains (i.e., social withdrawal and spatial learning deficits). Such a failure appears to be related to the ineffectiveness of the reconsolidation-extinction procedure in targeting the pathogenic process of fear sensitization, a nonassociative component of traumatic memory that causes animals to react aberrantly to harmless stimuli. This indicates fear sensitization as a major target for treatments aimed at mitigating anxiety and the behavioral outcomes of traumatic experiences.
authors.affiliation: CNR-National Research Council of Italy (Cell Biology and Neurobiology Institute-IBCN)/IRCCS Fondazione Santa Lucia, Rome 00143, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Costanzi
authors.forename: Sara
authors.initials: S
authors.lastname: Cannas
authors.forename: Daniele
authors.initials: D
authors.lastname: Saraulli
authors.forename: Clelia
authors.initials: C
authors.lastname: Rossi-Arnaud
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cestari
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D001362:Avoidance Learning; D001522:Behavior, Animal; D003214:Conditioning, Classical; D004195:Disease Models, Animal; D004597:Electroshock / Q000009:adverse effects; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D008297:Male; D018782:Maze Learning; D011939:Mental Recall / Q000502:physiology*; D051379:Mice; D011897:Random Allocation; D011930:Reaction Time / Q000502:physiology; D012919:Social Behavior; D013313:Stress Disorders, Post-Traumatic / Q000209:etiology / Q000503:physiopathology*