Influência do sexo e do ciclo hormonal nos efeitos agudos da fluoxetina na memória e comportamentos relacionados à ansiedade e depressão em ratos

Abstract

Depressive and stress and trauma-related disorders, which have great incidence among world population, present high comorbidity. Besides the respective emotional characteristics, individuals affected by these pathologies present important cognitive alterations. The first line of pharmacological treatment for both depressive and, to some extent, stress and trauma-related disorders are the antidepressants, mainly selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Even though women are approximately twice more affected by these disorders than men, the pre-clinical research on the effects of antidepressants on this sex is not as representative as in male subjects. Further, possible influences of the natural female hormonal cycle on the action of these drugs have been poorly explored. Our study aimed to investigate the acute effects of three doses of fluoxetine on the behavior of female rats at different phases of the estrous cycle, using the plus-maze discriminative avoidance task (PMDAT). The PMDAT is held in a modified elevated plus-maze that allows concomitant evaluation of cognitive and emotional parameters. Fluoxetine (5, 10 and 20mg/ml/kg) or vehicle were given i.p. to female rats at diferent cycle phases before training, after training or before testing. Animals were tested and retested 24h and 48h after the training session, respectively. Depressive-like behavior was also evaluated by the forced swimming test. Overall, the memory results showed that the effects of fluoxetine on female behavior varied according to the estrous cycle phase and period of administration. In addition, memory deficits, anxious- and depressive-like behaviors were observed in female rats after fluoxetine treatment. Despite clinical and animal studies show antidepressant and anxiolytic beneficial effects of fluoxetine prolonged treatment, the present results suggest possible cognitive and emotional acute side effects which may be influenced by sex and hormonal state.