title: Xenon impairs reconsolidation of fear memories in a rat model of post-traumatic stress disorder (PTSD).
abstract: Xenon (Xe) is a noble gas that has been developed for use in people as an inhalational anesthestic and a diagnostic imaging agent. Xe inhibits glutamatergic N-methyl-D-aspartate (NMDA) receptors involved in learning and memory and can affect synaptic plasticity in the amygdala and hippocampus, two brain areas known to play a role in fear conditioning models of post-traumatic stress disorder (PTSD). Because glutamate receptors also have been shown to play a role in fear memory reconsolidation--a state in which recalled memories become susceptible to modification--we examined whether Xe administered after fear memory reactivation could affect subsequent expression of fear-like behavior (freezing) in rats. Male Sprague-Dawley rats were trained for contextual and cued fear conditioning and the effects of inhaled Xe (25%, 1 hr) on fear memory reconsolidation were tested using conditioned freezing measured days or weeks after reactivation/Xe administration. Xe administration immediately after fear memory reactivation significantly reduced conditioned freezing when tested 48 h, 96 h or 18 d after reactivation/Xe administration. Xe did not affect freezing when treatment was delayed until 2 h after reactivation or when administered in the absence of fear memory reactivation. These data suggest that Xe substantially and persistently inhibits memory reconsolidation in a reactivation and time-dependent manner, that it could be used as a new research tool to characterize reconsolidation and other memory processes, and that it could be developed to treat people with PTSD and other disorders related to emotional memory.
authors.affiliation: Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, Massachusetts, United States of America.
authors.forename: Edward G
authors.initials: EG
authors.lastname: Meloni
authors.affiliation: Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, Massachusetts, United States of America.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Gillis
authors.affiliation: Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, Massachusetts, United States of America.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Manoukian
authors.affiliation: Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, Massachusetts, United States of America.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Kaufman
mesh_terms: D000679:Amygdala / Q000187:drug effects; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D003463:Cues; D004195:Disease Models, Animal; D004644:Emotions / Q000502:physiology; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear / Q000187:drug effects* / Q000523:psychology; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D014149:Tranquilizing Agents / Q000494:pharmacology*; D014978:Xenon / Q000494:pharmacology*
chemical_list: D014149:Tranquilizing Agents; D014978:Xenon