ABSTRACT
Objective: To evaluate whether exposing rats to individual or combined environmental stressors triggers endophenotypes related to mood and anxiety disorders, and whether this effect depends on the nature of the behavior (i.e., innate or learned). Methods: We conducted a three-phase experimental protocol. In phase I (baseline), animals subjected to mixed schedule of reinforcement were trained to press a lever with a fixed interval of 1 minute and a limited hold of 3 seconds. On the last day of phase I, an open-field test was performed and the animals were divided into four experimental groups (n=8/group). In phase II (repeated stress), each group was exposed to either hot air blast (HAB), paradoxical sleep deprivation (PSD) or both (HAB+PSD group) on alternate days over a 10-day period. Control group animals were not exposed to stressors. In phase III (post-stress evaluation), behavior was analyzed on the first (short-term effects), third (mid-term effects), and fifth (long-term effects) days after repeated stress. Results: The PSD group presented operant hyperactivity, the HAB group presented spontaneous hypoactivity and anxiety, and the HAB+PSD group presented spontaneous hyperactivity, operant hypoactivity, impulsivity, loss of interest, and cognitive impairment. Conclusion: A combination of environmental stressors (HAB and PSD) may induce endophenotypes related to bipolar disorder.