Anisomycin, a Protein Synthesis Inhibitor, Disrupts Traumatic Memory Consolidation and Attenuates Posttraumatic Stress Response in Rats

• Published in: Biological psychiatry (1969) 2006-10, Vol.60 (7), p.767-776
• Main Authors: Cohen, Hagit, Kaplan, Zeev, Matar, Michael A., Loewenthal, Uri, Kozlovsky, Nitsan, Zohar, Joseph
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Analysis of Variance; Animal model; Animals; Anisomycin - administration & dosage; anxiety; Anxiety - etiology; Anxiety - metabolism; Anxiety - prevention & control; Anxiety disorders. Neuroses; Association Learning - drug effects; Avoidance Learning - drug effects; Biological and medical sciences; Disease Models, Animal; Injections, Intraventricular; Male; Medical sciences; Memory - drug effects; memory consolidation; Microinjections; Post-traumatic stress disorder; posttraumatic stress disorder; Protein Synthesis Inhibitors - administration & dosage; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Sprague-Dawley; reactivation; reconsolidation; Reflex, Startle - drug effects; Stress Disorders, Post-Traumatic - etiology; Stress Disorders, Post-Traumatic - metabolism; Stress Disorders, Post-Traumatic - prevention & control; Stress, Psychological - complications; Stress, Psychological - metabolism
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2006.03.013

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. 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. 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. Disruption of the process of traumatic memory consolidation may be useful for mitigating PTSD symptoms.