[en] Clinical studies have shown that post-traumatic stress disorder (PTSD) remission, induced by selective serotonin reuptake inhibitor (SSRI) treatment, is associated with increased prefrontal activation during post-treatment symptom provocation. Other studies have shown that continuation SSRI treatment after remitting from PTSD reduces the rate of relapse. The aim of the present preclinical study was to investigate the relationship between post-treatment prefrontal changes and PTSD relapse prevention. Avoidance conditioning (with a 1.5-mA foot-shock), avoidance extinction and a trauma priming exposure (with a 0.3-mA foot-shock) were used in mice to induce, suppress and reactivate PTSD-like symptoms (including avoidance, fear sensitization, enhanced contextual fear, and anxiety-like behavior), respectively. Paroxetine, injected at 8 mg/kg/day (7 days), was used as SSRI treatment. PTSD-like symptoms were present for at least 30 days and resistant to paroxetine treatment. However, after extinction training (suppressing all PTSD-like symptoms), paroxetine treatment prevented symptom reactivation. Paroxetine treatment also induced infralimbic neuronal activation. However, infralimbic functional tetrodotoxin inactivation abolished the preventive effect of paroxetine treatment on symptom reactivation. The data reveal a potential ability of treatments inducing infralimbic activation to provide prophylactic protection against PTSD relapse.
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