Post-extinction fluoxetine treatment prevents stress-induced reemergence of extinguished fear

The post-extinction exposure of rats to a sub-conditioning procedure (SCP; i.e., retraining with a shock intensity that is too weak to induce by itself significant fear conditioning) has been reported to provoke the reemergence of extinguished fear. This phenomenon can be prevented by chronic fluoxetine treatment. We sought to examine another potential inducer of fear reemergence, acute stress, in rats and determine whether fluoxetine prevents this phenomenon. Because in previous studies fluoxetine was administered before extinction, we first analyzed its effect on the SCP-associated reemergence of auditory-cued conditioned fear in rats injected after extinction to avoid any interaction between fluoxetine and extinction learning. Next, we used the same protocol but replaced the SCP with acute stress. We found that the SCP and acute stress, which were carried out 3 weeks after fear extinction, similarly provoked the reemergence of extinguished fear in rats injected with vehicle during the 3-week period. In contrast, the animals treated with fluoxetine during this period behaved similarly to those not exposed to an inducer of fear reemergence. Our data establish acute stress as an inducer of fear reemergence. The results provide further support for the hypothesis that fluoxetine interfered with mechanisms that reactivated extinguished fear, even when administered after fear extinction.