Prefrontal high-frequency stimulation prevents sub-conditioning procedure-provoked, but not acute stress-provoked, reemergence of extinguished fear

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• Post-extinction exposure to a sub-conditioning procedure is known to reactivate extinguished fear. • Here, we found that this fear reactivation was prevented by prefrontal tetanic stimulation. • Prefrontal tetanic stimulation failed to prevent fear reactivation when it was provoked by acute stress.

We have recently shown that 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) or to acute stress provokes reemergence of extinguished fear. Furthermore, this SCP effect can be abolished by high-frequency stimulation (HFS) of the medial prefrontal cortex (mPFC), when applied following the SCP. The aim of the present study was to test whether HFS of the mPFC is effective in preventing both SCP-induced and acute stress-provoked fear reemergence. Rats implanted with stimulating electrodes in the mPFC were trained to acquire high levels of freezing to conditioned auditory cue. This fear response was then extinguished. Three weeks later, no spontaneous recovery was observed, but rats exposed to either the SCP or acute stress again exhibited high levels of freezing. HFS of the mPFC, applied before provoking fear reemergence, prevented the effects of SCP, but not acute stress. These data suggest that acute stress may have more impact on functions of the mPFC and/or associated structures than a situational reminder of fear conditioning.

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