Resumo

The antidepressants utilized to treat major depression, posttraumatic stress disorder and others psychopathologies are usually associated with improvement of the cognitive deficits caused by these disorders. However, the mechanisms of these effects are not completely elucidated. Moreover, the effects of the antidepressants in women are not totally understood because researches with laboratory animals usually focus on male subjects. In the present study, we treated female rats with some clinically used antidepressants and tested them in the plus-maze discriminative avoidance task and forced swimming test in order to evaluate memory, anxiety and depression-related behaviors. Three-month-old group-housed female Wistar rats (120–230g) were maintained on a 12-h light/dark cycle with food and water freely available. We allocated animals to one of four groups: (a) treated with selective serotonin reuptake inhibitor (SSRI), fluoxetine, (b) tricyclic antidepressant, nortriptyline, both in a dose of 20mg/ml/kg daily, (c) an atypical antidepressant, mirtazapine, in a dose of 10mg/ml/kg daily, and (d) vehicle, saline with tween, all injected via intraperitoneal. The injections and estrous cycle control (by analysis of vaginal smear) were held for sixteen consecutive days at 6 p.m.. On the 17° day, behavioral tests started at 1:30 p.m. (injections continued throughout testing) . First, animals were tested on the plus-maze discriminative avoidance task that consists of two open arms e two closed arms, in one of which aversive stimuli (light and noise) were presented in the training session. A test session, without aversive stimuli, was performed 24h later. Afterwards, same animals were tested in the forced swimming test. Animals treated with mirtazapine exhibited a significant decreased locomotor activity (distance travelled – m) on training (vehicle 19±2.4; mirtazapine 10.4±0.5; p<0.01) and test session (vehicle 21.1±1.9; mirtazapine 8.5±2.3; p<0.01) of the maze. The exploration of the aversive arm was equal in training session, showing that all groups learned the task. Task retrieval low aversive arm exploration in the beginning of test session was also showed by all experimental groups. However, differences were found in extinction of the task. Extinction index in each group was quantified by the percentage of animals that spent more than 40% of time in the aversive arm during the 10th minute. The results showed that fluoxetine increased, while mirtazapine decreased extinction of the task (vehicle 30%; fluoxetine 56%; nortriptyline 38%; mirtazapine 13%). In the forced swimming test animals treated with fluoxetine and mirtazapine showed decreased immobility (p&le0.05) compared with vehicle and nortriptyline (vehicle 125.2±15; fluoxetine 59.1±8; nortriptyline 92.1±19.8; mirtazapine 66±6.3). Rats form all groups learned and retrieved the task, but female rats treated with fluoxetine presented increased extinction of the aversive memory task. This is in line with the efficacy of this drug in the treatment of posttraumatic stress disorder (Cabe et al, Biol Psychiatry, 67:439–445; 2010). On the other hand, both fluoxetine and mirtazapine were effective in the forced swimming test, suggesting a dissociation between antidepressant effects and extinction of aversive memories.