Person:

Meloni, Edward

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.

Posttraumatic stress disorder (PTSD) is a debilitating disease with limited available treatment options and for which novel effective interventions constitute a significant unmet need. This case report describes successful treatment of a patient with panic disorder and PTSD stemming from the 2010 Moscow subway terrorist attacks through the combination of script-driven trauma memory reactivation and inhalation of a xenon-based gas mixture. Xenon is a competitive inhibitor of N-methyl-d-aspartate receptors known to play a role in memory reconsolidation, a learning and memory process wherein memories temporarily enter a labile state after reactivation and may be modified. Literature describing current pharmacologic and exposure-based treatments is reviewed and provides the basis for use of this novel treatment strategy to target and modify emotional memories.