Recent fear is resistant to extinction - PubMed (original) (raw)

Recent fear is resistant to extinction

Stephen Maren et al. Proc Natl Acad Sci U S A. 2006.

Abstract

In some individuals, fearful experiences (e.g., combat) yield persistent and debilitating psychological disturbances, including posttraumatic stress disorder (PTSD). Early intervention (e.g., debriefing) after psychological trauma is widely practiced and argued to be an effective strategy for limiting subsequent psychopathology, although there has been considerable debate on this point. Here we show in an animal model of traumatic fear that early intervention shortly after an aversive experience yields poor long-term fear reduction. Extinction trials administered minutes after aversive fear conditioning in rats suppressed fear acutely, but fear suppression was not maintained the next day. In contrast, delivering extinction trials 1 day after fear conditioning produced an enduring suppression of fear memory. We further show that the recent experience of an aversive event, not the timing of the extinction intervention per se, inhibits the development of long-term fear extinction. These results reveal that the level of fear present at the time of intervention is a critical factor in the efficacy of extinction. Importantly, our work suggests that early intervention may not yield optimal outcomes in reducing posttraumatic stress, particularly after severe trauma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

Fig. 1.

Immediate or delayed extinction after fear conditioning. (A) Freezing behavior on the conditioning day. Data are 1-min averages for the period before (baseline, BL) and after each of five tone–shock conditioning trials. (B) Freezing behavior during the extinction session, which occurred either 15 min (IMMED) or 24 h (DELAY) after conditioning. Control rats did not receive CS presentations during extinction (NO-EXT). (C) Freezing behavior during the retention test 48 h after conditioning. (D) Baseline freezing data were averaged and subtracted from the average freezing across test trials to yield normalized freezing for the retention test data shown in C. All data are means ± SEM. ∗, P < 0.05.

Fig. 2.

Fig. 2.

Retention testing with a common extinction test interval. Shown is freezing behavior during the retention test 48 h after extinction. The extinction test interval was equated in rats that were extinguished either 15 min (IMMED) or 24 h (DELAY) after conditioning. Control rats did not receive CS presentations during extinction (NO-EXT). Data were normalized as in Fig. 1_D_. All data are means ± SEM. ∗, P < 0.05.

Fig. 3.

Fig. 3.

Massed or distributed extinction trials immediately after fear conditioning. Rats received 45 or 225 extinction trials 15 min after fear conditioning. For two groups of rats (EXT45–12 and EXT225–12), the extinction trials were massed (12-sec ISI). The EXT45–60 group was treated identically to that in Experiment 1 (45 trials; 60-sec ISI). Total time in the extinction context was equated in all of the groups. The graph displays freezing behavior during the retention test 24 h after extinction. Data were normalized as in Fig. 1_D_. All data are means ± SEM.

Fig. 4.

Fig. 4.

Reducing fear before immediate extinction. (A) Freezing behavior on the conditioning day. Data are 1-min averages for the periods before (baseline, BL) and after a single tone–shock conditioning trial. (B) Freezing behavior during the extinction session in a novel context, which occurred either 15 min (IMMED) or 24 h (DELAY) after conditioning. Control rats were exposed to the context but did not receive CS presentations during extinction (NO-EXT). (C) Freezing behavior during the retention test 48 h after conditioning; data from the retention test were normalized as in Fig. 1_D_. All data are means ± SEM. ∗, P < 0.005.

Fig. 5.

Fig. 5.

Arousing fear before delayed extinction. (A) Freezing behavior on the conditioning day. Data are 1-min averages for the periods before (baseline, BL) and after each of five tone–shock conditioning trials. (B) Freezing behavior during the extinction session. Extinction training was conducted in the context in which the rats had been conditioned a day earlier. Fifteen minutes before the extinction session, rats received either five unsignaled footshocks (SHOCK) in a novel context or exposure without shock (NO-SHOCK) in that context. Control rats did not receive CS presentations during extinction (NO-EXT). (C) Freezing behavior during the retention test 48 h after conditioning. All data are means ± SEM. ∗, P < 0.05.

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