Effects of fluoxetine on estrous cycle and sexual behavior in female rats

Although highly effective for treatment of depression, antidepressants, such as fluoxetine (Prozac®), produce sexual dysfunction in a substantial number of patients. Mechanisms responsible for such sexual dysfunction were the focus of these studies. In a previous experiment, when female Fischer rats were treated daily with 10 mg/kg fluoxetine, both the estrous cycle and sexual behavior were disrupted. These results contrast with prior findings from which it has been suggested that fluoxetine does not disrupt estrous cyclicity. The current studies were designed to investigate explanations for the different outcomes and identify mechanisms for the cycle disruption. Fischer female rats received 15 days of 10 mg/kg fluoxetine with or without a 5 min daily exposure to a sexually active male. Male exposure delayed the onset of cycle disruption. Sprague-Dawley females were treated daily with 10 mg/kg fluoxetine to examine the generality of prior findings. Cycle disruption, though present, was less severe than in Fischer rats. A pair-fed group was added to the protocol to determine if reduced food intake contributed to the fluoxetine-induced sexual disruption in Fischer females. Pair-feeding mimicked the effect of fluoxetine on the estrous cycle. In the next experiment, we questioned if hormonal priming could prevent the effect of fluoxetine on sexual behavior as measured by the lordosis reflex. In spite of hormonal priming, fluoxetine still reduced lordosis behavior. However, the magnitude of disruption was less than that seen in intact females. Finally we examined the effects of repeated fluoxetine treatment on serum luteinizing hormone (LH) both in ovariectomized and intact rats. Fluoxetine treatment failed to show any significant effect on serum LH. These experiments reinforce the possibility that a fluoxetine-induced disruption of the estrous cycle contributes to the drug-induced sexual dysfunction.