Sex-dependent effects of fluoxetine and triiodothyronine in the forced swim test in rats

The effects of triiodothyronine (T3) and fluoxetine, administered separately and combined, on behavior of mate and female rats in the forced swim test, a procedure for screening antidepressant-like activity, were determined. There were no consistent effects of tow doses of fluoxetine (5 mg/kg) or T3 (20 mu g/kg), administered daily for 2 weeks. Fluoxetine administered daily at 10 mg/kg for 7 days reduced immobility and increased active behaviors in mate rats, but had no effects in female rats. The effects of fluoxetine in mate rats were not potentiated by T3. In female rats, T3 at 100 mu g/kg given daily for 7 days decreased immobility and increased swimming when these were measured 72 h after the last injection, but not when measurements were performed at an earlier time point. These results provide some support from an animal model for the efficacy of T3 as antidepressant therapy in female patients, but do not provide support for the augmentation and acceleration effects seen clinically when T3 is used in conjunction with established antidepressants such as fluoxetine. (c) 2005 Elsevier B.V. and ECNR All rights reserved.