Subchronic treatment with fluoxetine attenuates effects of acute fluoxetine on female rat sexual behavior.

These experiments were designed to evaluate the hypothesis that fluoxetine-induced sexual dysfunction in female rats derived from disruption of neuroendocrine events that normally facilitate sexual behavior. If so, exogenous hormonal priming to ovariectomized rats should eliminate fluoxetine's effect. Ovariectomized rats were subchronically treated with 10 mg/kg fluoxetine or distilled/deionized water vehicle for 9 consecutive days. On the 8th day of treatment, rats were primed with 10 microg estradiol benzoate followed 48 h later with 500 mug progesterone. In a pretest for sexual behavior on the 10th day, there was no difference between subchronic treatments. Sexual receptivity was again monitored 30 min after injection on the 10th day (acute treatment) with distilled/deionized water, 10 mg/kg fluoxetine or 20 mg/kg fluoxetine. Thereafter, the female's behavior was monitored for 20 min in a male preference procedure. After the acute treatment in rats subchronically treated with water, fluoxetine (10 or 20 mg/kg) significantly reduced both lordosis frequency and quality and reduced (but not significantly) time spent with the male. In rats subchronically treated with fluoxetine, the lordosis-inhibiting effect of an acute injection with fluoxetine was significantly attenuated relative to that of the subchronically water-treated rats. In contrast to expectation, subchronic treatment with fluoxetine increased, rather than reduced, the relative time females spent near the male. Activity, as measured by center crossings, and grooming were also reduced by subchronic treatment with fluoxetine.