Chronic treatment with fluoxetine prevents the return of extinguished auditory-cued conditioned fear

Rationale We have recently shown that post-extinction exposure of rats to a sub-threshold reminder shock can reactivate extinguished context-related freezing and found that chronic treatment with fluoxetine before fear extinction prevents this phenomenon. Objectives In the present study, we examined whether these findings would be confirmed with auditory fear conditioning. Methods Rats were initially submitted to a session of five tone-shock pairings with either a 0.7- or 0.1-mA shock and underwent, 3 days later, a session of 20 tone-alone trials. Results At the beginning of this latter session, we observed cue-conditioned freezing in rats that received the strong, but not the weak, shock. At the end, both groups (strong and weak shocks) displayed similar low levels of freezing, indicating fear extinction in rats exposed to the strong shock. These rats exhibited again high levels of cue-evoked freezing when exposed to three tone-shock pairings with 0.1-mA shock. This reemergence of cue-conditioned fear was completely abolished by chronic (over a 21-day period) fluoxetine treatment which spared, when administered before the initial fear conditioning, the original tone-shock association. Conclusions These data extend our previous findings and suggest that chronic fluoxetine treatment favor extinction memory by dampening the reactivation of the original tone-shock association.