In despite the similarity of mechanisms of action between both selective serotonin reuptake inhibitors (SSRI) and MDMA (main compound of “Ecstasy”) there are relatively few reports on the effects of the later on animal models of depression. There are many animal models designed to create or to assess depression. Mild chronic stress (MCS) is a procedure designed to create depression. MCS includes the chronic exposure of the animal to several stressors. After that, rats show behavioural changes associated to depression. In the other hand, the active avoidance task (AAT) is an experimental situation in which an animal has to accomplish a particular behaviour in order to avoid the application of a stressor. Animals exhibiting depression fail to acquire avoidance responses as rapidly as normal animals do. In order to assess the effect of MDMA on the acquisition of an active avoidance response, forty-five rats were divided in two groups exposed or not exposed to MCS. Rats also received chronic intracerebroventricular MDMA (0.2 μg/μl; 1 μl), fluoxetine (2.0 μg/μl; 1 μl) or saline solution (0.9%; 1 μl). Our results showed that the effect of MDMA depends upon the level of stress. MDMA treated animals showed better acquisition (F[2,37] = 7.046; P = 0.003) and retention (F[2,37] = 3.900; P = 0.029) of the avoidance response than fluoxetine or saline treated animals when exposed to MCS. This finding suggests that MDMA (and no fluoxetine) was able to change the aversive valence of the stressors maybe enhancing coping strategies. This effect could serve as a protective factor against helplessness and maybe post-traumatic stress.