Factors influencing fluoxetine-induced sexual dysfunction in female rats.

Treatment with selective serotonin reuptake inhibitors, such as fluoxetine, produces sexual side effects with low sexual desire being the most prevalent effect in females. In few studies have preclinical models for such antidepressant-induced sexual dysfunction been fruitful. In the current manuscript, the effects of fluoxetine on multiple measures of female sexual motivation and sexual receptivity were examined. Ovariectomized, Fischer rats were primed with 10 µg estradiol benzoate and 500 µg progesterone. Partner preference, active investigation of the male, and measures of sexual behavior were examined after injection with 15 mg/kg fluoxetine. Factors (pretesting for sexual behavior, size of the test arena, non-contact time with a male) that differ among experiments designed to study antidepressant-induced female rat sexual dysfunction were studied. The male preference ratio was not affected by fluoxetine treatment but active investigation of the male was reduced; lordosis behavior was inhibited and pretesting for sexual receptivity amplified fluoxetine's inhibition; size of the testing arena or non-contact experience with the male had no effect. Regardless of test condition, when given the opportunity to escape from the male, fluoxetine-treated females displayed escape behavior. Measures of male preference and active investigation, but not lordosis behavior, appeared to be affected by fluoxetine's impact on activity. The collective data provided a behavioral profile of fluoxetine-induced sexual dysfunction. These findings reinforce the value of multiple measures when attempting to model antidepressant-induced female sexual dysfunction.

Tropisetron increases the inhibitory effect of mild restraint on lordosis behavior of hormonally primed, ovariectomized rats.

Ovariectomized rats, hormonally primed with 10 µg estradiol benzoate and 500 µg progesterone are resistant to the lordosis-inhibiting effects of a 5 min restraint experience. However, modulation of the serotonergic (5-HT) system alters this resistance to stress. In the following experiment, ovariectomized Fischer inbred rats were hormonally primed with 10 µg estradiol benzoate and 500 µg progesterone. The effect of 5 min restraint on sexual behavior was examined after bilateral hypothalamic infusion or intraperitoneal (ip) treatment with the 5-HT(3) receptor antagonist, 3-tropanylindole-3-carboxylate hydrochloride (tropisetron). Infusion with 50 or 100 ng tropisetron inhibited lordosis behavior. When rats were infused with 10 or 25 ng tropisetron, rats showed normal lordosis behavior. However, when infusion with 10 or 25 ng tropisetron was combined with 5 min restraint, lordosis behavior was inhibited. These findings are consistent with prior work that has implicated hypothalamic serotonin in control of lordosis behavior and in the effect of mild restraint on the behavior. In contrast to the effects of the intracranial infusion, intraperitoneal injection with 1.0 or 2.0 mg/kg tropisetron did not amplify the effects of restraint.