Ethopharmacology of imipramine in the forced-swimming test: gender differences

Most of the pre-clinical tests used to assay the efficacy of prospective new agents are done with male experimental animals. In this case, a large part of the population is disregarded as is the interaction of the new agent's effects with female hormonal fluctuations. The present study reviews the technical procedures characteristic for the forced-swimming test and the behavioral outcome induced by the testing procedure in males. It also compares the anti-immobility effects of the classic antidepressant imipramine (IMI) in male and female rats using a detailed behavioral scoring. Female rats had vaginal smears done before the beginning of the behavioral testing and were administered with three doses 24 h, 5 h and 1 h before the retest, as were male rats. Tests were videotape-recorded for analysis of the frequency and duration of the behaviors during forced-swimming. Male rats spend around 50% of the time immobile during the retest. There was a significant, dose-dependent decrease in immobility duration and a decrease in head-shakes of male rats treated with IMI. Both active behaviors of climbing and swimming were equally enhanced by the tricyclic antidepressant, climbing behavior comprising 75% of the mobile behaviors. Females showed much lower immobility duration and head-shake frequency during the forced-swimming than males and spent longer periods in mobile behaviors. Imipramine only decreases immobility frequency and head-shakes of females, and increases the escape-type behavior of climbing, decreasing swimming in the middle of the tank. This effect is more noticeable during estrus and proestrus. These results demonstrate the main behavioral differences between males and females in the forced-swimming test. It also elucidates that the effects of imipramine are measurable in males using the duration of the behaviors, while the frequencies of behaviors are modified in females treated with imipramine.