Pre-training administration of tianeptine blocked the effects of predator stress on spatial memory in adrenalectomized (ADX) and adrenal-intact (Sham) rats without affecting corticosterone levels. Arm entry errors from the 12 acquisition trials in the RAWM (data not shown) were analyzed with a mixed-model ANOVA. This analysis revealed significant main effects of trials, F(11,693) = 19.59, and drug, F(1,63) = 4.28, and a significant Surgery x Stress x Drug interaction, F(1,63) = 4.18 (p’s < 0.05). While all groups made significantly fewer arm entry errors as trials progressed, tianeptine led to significantly more arm entry errors than vehicle in all groups except for the stress-exposed ADX group. All other main effects and interactions were not significant. Arm entry errors from the 30 min memory test trial (left) were analyzed with a one-way ANOVA. This analysis revealed significant main effects of stress, F(1,63) = 20.64, and drug, F(1,63) = 9.22, as well as a significant Stress x Drug interaction, F(1,63) = 18.22 (p’s < 0.01). Vehicle-treated rats exposed to predator stress during the 30 min delay period made significantly more arm entry errors than control (i.e., unstressed) rats. The administration of tianeptine prior to training blocked this effect in both ADX and sham-operated animals. Serum corticosterone levels (right) were analyzed with a one-way ANOVA. This analysis revealed significant main effects of surgery, F(1,41) = 129.71, and stress, F(1,41) = 49.75, and a significant Surgery x Stress interaction, F(1,41) = 46.08 (p’s < 0.0001). Water maze training significantly increased corticosterone levels in sham-operated control rats, relative to ADX controls. Predator stress significantly increased corticosterone levels in sham-operated, but not ADX, rats, an effect that was independent of tianeptine treatment. For the water maze data, the dashed line at 2.5 errors indicates chance level of performance [40]. * = p < 0.05 relative to no stress groups and tianeptine-treated stress groups; β = p < 0.05 relative to stress groups and ADX-no stress groups; # = p < 0.05 relative to no stress groups and ADX-stress groups.