Depression is the most common mood disorder affecting humans, mainly females. It is normally treated with a class of drugs called antidepressants. However, researches with laboratory animals usually focus on male subjects. Thus, most of the drug effects and mechanisms are not tested in females. In addition, depression has been related to both cognitive features and anxiety levels.

Our research aimed to evaluate the effects of two types of antidepressants on memory and anxiety on female rats. Three-month-old group-housed female Wistar rats (120-210g) were maintained on a 12-h light/dark cycle with food and water freely available. We allocated animals to three groups: (a) treated with selective serotonin reuptake inhibitor (SSRI), fluoxetine, (b) tricyclic antidepressant, nortriptyline, both in a dose of 20mg/ml/kg daily  and (c) vehicle, all injected via intraperitoneal. The injections and estrous cycle control (by analysis of vaginal smear) were done for sixteen consecutive days at 6 p.m.. On the 17° day, behavioral tests, started at 1:30 p.m. and injections continued at the same time. In order to evaluate the effects of the antidepressants on memory and anxiety we used the plus-maze discriminative avoidance task: the animals was placed on a elevate plus-maze with two open arms e two closed arms, in one of which aversive stimuli (light and noise) were presented in the training session. For evaluation the effect of the antidepressants we used the forced swimming test.

In the trial session both groups treated with antidepressants showed increased anxiety evidenced by the decreased rate of the open arms exploration,(fluoxetine 12,0±3,5; nortriptyline 12,4±4,9; vehicle 22,9±6,1). There were no differences among groups in learning (decreasing of aversive arm exploration throughout the training). In the test session animals treated with nortriptyline showed less general activity, evaluated by the distance traveled, (nortriptyline 16,8±4,4; fluoxetine 21,6±4,4; vehicle 27,5±4,4) and less aversive arm exploration in comparison with other groups (nortriptyline 9,9±5,1; fluoxetine 22,8±6,4; vehicle 21,0±6,8). The results showed an increase on anxiety caused by the antidepressant treatment. Commonly, males treated with antidepressants exhibit decreased anxiety being that one of the reasons to use antidepressant in anxiety disorders. These drugs did not affect the learning and memory on females in the present study.

It will be necessary more studies to better evaluate the effects of antidepressant treatment in females on the plus-maze discriminative avoidance task. Moreover, other antidepressant classes must be evaluated in this apparatus to confirm the anxiogenic effect observed here in with antidepressant drugs.