Figure 2. Chronic but not subchronic tianeptine treatment impairs the acquisition of fear extinction.

(A) General behavioral procedures: 24 hours after habituation, rats were fear conditioned with two tone-shock pairings. The next day, animals began treatment with tianeptine (10 mg/kg, i.p.) or saline. Chronic treatment lasted for 22 consecutive days. Subchronic treatment lasted for 9 consecutive days. Extinction training began the same day the final injection was administered and involved 20 presentations of the tone alone over the course of two days. (B–D) The effects of chronic tianeptine treatment on extinction learning. (B) Mean ± SEM percent freezing of tianeptine-treated (n=24) and saline-treated (n=23) rats during each trial of extinction training. The average response of each group was not significantly different during tone 1, indicating that chronic tianeptine treatment did not affect expression of the fear memory. (C) Mean ± SEM percent freezing of each group averaged across the first 10 tones, which were presented on the first day of extinction training. (D) Mean ± SEM percent freezing of each group averaged across the last 10 tones, which were presented on the second day of extinction training. (E–G) The effects of subchronic tianeptine treatment on extinction learning. (E) Mean ± SEM percent freezing of tianeptine-treated (n=21) and saline-treated (n=24) rats during each trial of extinction training. Tianeptine-treated rats exhibited significantly less tone-elicited freezing than saline-treated rats during the first tone trial, indicating that subchronic tianeptine treatment reduced fear expression (p<0.01). (F) Mean ± SEM percent freezing of each group averaged across the first 10 tones, which were presented on the first day of extinction training. (G) Mean ± SEM percent freezing of each group averaged across the last 10 tones, which were presented on the second day of extinction training. *p<0.01 versus saline.