Sex differences in behavioral, neurochemical and neuroendocrine effects induced by the forced swim test in rats

The forced swim test (FST) has been considered as a pharmacologically valid test of the depressive syndrome in rodents. However, few studies have focused on neurochemical and behavioral responses during FST in both male and female rats. Thus, we investigated certain behavioral and neuroendocrine responses as well as the serotonergic activity after the application of FST in both sexes. Our data show that the duration of immobility was increased in both male and female rats during the 2nd session of the FST. Sex differences are observed in some behavioral responses, such as head swinging that is mostly present in male rats. In female rats FST induced a decrease in serotonergic activity in hippocampus and hypothalamus while in male rats it induced an increase in serotonergic activity in hypothalamus. Corticosterone serum levels were elevated in both sexes. However, hippocampal GR mRNA levels tended to be increased in males and females respectively. Moreover, hypothalamic serotonin (5-HT)1A mRNA levels were decreased in female rats while in male rats hippocampal 5-HT1A mRNA levels were increased. These data have shown that FST induces "depressive like symptoms" in both sexes and provide evidence that sex differences characterize certain behavioral aspects in the FST. Notably, hippocampal and hypothalamic serotonergic activity has been differentially modified in male rats compared with female rats and these neurochemical findings could be relevant to the differentiated expression of 5-HT1A receptor. Hypothalamic-pituitary-adrenal axis activity was also affected by FST application in a sex specific manner. The present results support that FST induced behavioral, neurochemical and neurobiological alterations, which are sex dependent.