Anisomycin, a protein synthesis inhibitor, disrupts traumatic memory consolidation and attenuates posttraumatic stress response in rats.
BACKGROUND
Paradoxical changes in memory represent a troublesome characteristic of posttraumatic stress disorder (PTSD). Exceptionally vivid intrusive memories of some aspects of the trauma are mingled with patchy amnesia regarding other important aspects. Molecular studies of the memory process suggest that the conversion from labile short-term memory into long-term fixed traces involves protein synthesis. This study assessed the effects of administration of anisomycin, a protein synthesis inhibitor, after initial exposure, after exposure to a cue associated with triggering experience, and after reexposure to the triggering trauma in an animal model of PTSD.


METHODS
Magnitude of changes in prevalence of anxiety-like behaviors on the elevated plus-maze and nonhabituated exaggerated startle reaction were compared in rats that were exposed to predator stress, with and without microinjection of anisomycin.


RESULTS
Microinjection of anisomycin before and after stress exposure reduced anxiety-like and avoidant behavior, reduced the mean startle amplitude, and reversed the stress-induced habituation deficit 7 days later. The persistent anxiety-like behaviors that were seen after stress exposure do not appear to be sensitive to anisomycin after reexposure to a cue associated with the event or after reexposure to the index experience.


CONCLUSIONS
Disruption of the process of traumatic memory consolidation may be useful for mitigating PTSD symptoms.
Cohen
Hagit
H
Ministry of Health Mental Health Center, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel. hagitc@bgu.ac.il
Kaplan
Zeev
Z
Matar
Michael A
MA
Loewenthal
Uri
U
Kozlovsky
Nitsan
N
Zohar
Joseph
J
D000704:Analysis of Variance; D000818:Animals; D000841:Anisomycin / Q000008:administration & dosage*; D001007:Anxiety / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D001245:Association Learning / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects*; D004195:Disease Models, Animal; D007276:Injections, Intraventricular; D008297:Male; D008568:Memory / Q000187:drug effects*; D008845:Microinjections; D011500:Protein Synthesis Inhibitors / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects; D013313:Stress Disorders, Post-Traumatic / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism*
D011500:Protein Synthesis Inhibitors; D000841:Anisomycin