Environmental enrichment is able to induce behavioral effects in rats and mice exposed to the forced swimming test as well as in the morphology of the central nervous system. Our aim was to evaluate the effects of environmental enrichment from weaning on behavioral output of control and antidepressants-treated adult rats in the repeated Forced Swimming Test (1). In addition, we investigated cell proliferation in the hippocampal dentate gyrus of these rats. Male Wistar rats (n=80) were housed for 40 days from postnatal day 21 in standard (SE) or enriched (EE) environment. After this period they were exposed to the Pre-test (day 1, 15 min of forced swimming). In the next day (day 2), rats were randomly assigned in one of 4 groups and 1 hour before the Test (i.e. 5 min of forced swimming) they received an intraperitoneal injection with saline (SAL), or imipramine (IMI, 2.5 or 5 mg/kg) or fluoxetine (FLX 2.5 mg/kg). A daily injection of these compounds was performed to the respective group from the day 3 (one day after the Test) until day 7 (the day of the Retest 1, i.e., 5 min of forced swimming) and until day 14 (the day of Retest 2, i.e., 5 min of forced swimming). Pre-test, Test and Retests 1 and 2 were videotaped for posterior analysis of behavior (latency, frequency, duration of immobility, swimming, climbing). Duration of immobility was considered an index of behavioral despair. After retest 2, rats were anesthetized and sacrificed for brain dissection and preparation for Ki-67 (proliferation marker) immunohistochemistry in hippocampal dentate gyrus. Effects of retesting were analyzed using repeated measures Anova. Between groups analysis were performed using One Way Anova. When appropriate post hoc Duncan’s test was performed. Housing in EE failed to affect behavior in the Pre-test or Test but attenuated the effects of re exposure on behavior of control rats. Antidepressants decreased the index of behavioral despair after 7 (Retest 1) and 14 (Retest 2) days of treatment as compared to saline in SE groups. The efficacy of FLX, not IMI, in reduce behavioral despair increased with the time (from Test to Retest 2) in SE groups. In EE groups, antidepressants (IMI 5 mg/kg and FLX 2.5 mg/kg) decreased the index of behavioral despair after 14 days of treatment (Retest 2) when compared to their effects after 1 day of treatment (Test). Surprisingly, these later treatments also decreased the counting of Ki-67 in the dentate gyrus as compared to saline. These data suggest that enriched environment improved the coping with forced swimming stress and improved the effects of chronic treatment with imipramine on behavioral despair in a fashion unrelated to the increased proliferation in dentate gyrus of adult rat hippocampus.