Resumo

Learned Helplessness (LH) is a classical animal model of depression based in impairment of avoidance to signalized escapable shocks (ES) after pre-exposure to inescapable footshocks (IS). These responses are attenuate/prevented by chronic treatment with antidepressant drugs, such as Imipramine (IMI), a 5-HT/NA reuptake blocker. Great attention is being given to ethical aspects involving animals in research, trying to minimize their suffering. Therefore, the aims of our work were: to validate an LH protocol (Experiment 1); and test whether chronic treatment with IMI would prevent LH in animals submitted to IS in the protocol defined in Experiment 1. The effects of chronic treatment with MK-801, an NMDA receptor antagonist, in this model were also investigated. Experiment 1: Male wistar rats (300g) were pre-exposed (PE) to protocols (P) with 40 IS or ES, which varied in intensity (0.6mA for P1 and P2 – or 0.4mA for P3) and duration in seconds (sec; 5 sec for P1 or 10 sec for P2 and P3). 24 hours later they received 30 ES (0.4mA or 0.2mA, respectively for P1/P2 and P3) signalized by a light stimulus (10 sec.) that remained on until the end of the shock. Shocks could be avoided/interrupted by crossing to the opposite side of the box. Control groups (P4, P5 and P6) received no shocks (NS) in PE. In Experiment 2 rats received 21 daily i.p. injections of Saline (1ml/kg; n=16); IMI (15mg/kg; n=17) or MK801 (0.05mg/kg; n=16) being the last injection immediately after pre-exposure to IS as in P2. Tests were performed 24 hours later. Helplessness (LH) was considered when number of failure to avoid/escape shocks was greater than 10. Percent of LH (%LH) animals per group were calculated and then analyzed by Chi-Square test. Pre-exposure to IS or ES (0.6mA; 5”) increased %LH (92% and 71%) when compared to NS (27%) during test session (0.4mA; 5sec) (X22=10.9; p<0.05). Decreasing the intensity of footshocks (IS or ES of 0.4mA) and increasing its duration (10sec.) induced similar results on %LH (50% for both conditions) when compared to NS rats (25%) (X22=0.7; p>0.05). On the other hand, keeping 0.6mA of intensity but increasing its duration up to 10sec did change the performance of animals: %LH were lower on ES or NS groups (17% each) than in IS (100%) (X22=71,9; p<0.05). Using this protocol chronic treatment with IMI prevented induction of LH (15%) when compared to Saline (83%) and MK801 (87,5%) treated rats (X22=17.2; p<0.05). Lower intensities of IS did not induce LH even when IS was longer in duration. IMI was able to prevent LH.