Strain Differences in Fluoxetine-Induced Sexual Dysfunction

The present experiments were designed to examine strain differences in sexual dysfunction after acute fluoxetine treatment. Female Fischer and Sprague-Dawley rats were used. Three major experiments were performed. (1) Strain differences were examined in regularly cycling female rats and in ovariectomized rats hormonally primed with 0.067 µg/g estradiol benzoate and 3.333 µg/g progesterone following treatment with 5, 10, 15, 20 or 30 mg/kg fluoxetine. (2) The effects of the 5-HT2 receptor antagonist, ketanserin 0.416, 0.5, 1, 2, 5 or 10 mg/kg, were compared in the two strains. (3) The combination of 10 mg/kg fluoxetine and l mg/kg ketanserin was examined. The major outcomes of this study were: (i) consistent with prior studies, fluoxetine reduced female rat sexual behavior in both hormonally-primed, ovariectomized and in naturally cycling rats; (ii) hormonally primed, ovariectomized rats were more sensitive to the lordosis inhibiting effects of fluoxetine than the intact, naturally cycling females; (iii) in both hormonally-primed and naturally cycling rats, Sprague-Dawley females were less sensitive to the lordosis-inhibiting effects of fluoxetine than Fischer females; (iv) a 5-HT2A/2C receptor antagonist, ketanserin, reduced lordosis behavior in both strains with a slightly greater effect in Sprague-Dawley females, but the difference was modest in comparison to the strain differences in response to either fluoxetine, and (v) the combination of fluoxetine and ketanserin did not amplify negative effects on lordosis behavior relative to the individual drugs alone. From these experiments, it was concluded that Fischer female rats are more sensitive than Sprague-Dawley females to the lordosis inhibiting effects of fluoxetine and that the 5-HT2 receptor, may not be involved. Potential mechanisms responsible for strain differences in the receptor activation are discussed.