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Comparative Study
. 2008 Jan 23:1190:56-64.
doi: 10.1016/j.brainres.2007.11.033. Epub 2007 Nov 28.

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

J Sarkar  1 , C Hiegel, G E Ginis, E Hilbun, L Uphouse
Affiliations
Comparative Study

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

J Sarkar et al. Brain Res. .

Abstract

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.

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Figures

Figure 1
Figure 1. Fluoxetine effects on lordosis frequency
Ovariectomized rats were subchronically treated with 10 mg/kg fluoxetine or the water vehicle. After a pretest for sexual receptivity, rats, hormonally primed with 10 μg estradiol benzoate and 500 μg progesterone, were injected with water, 10 mg/kg fluoxetine or 20 mg/kg fluoxetine. Sexual behavior testing occurred 30 min later. In 1A, data are the mean ± S.E. L/M ratios. N’s per treatment were 12, 7, and 15, respectively, for rats subchronically treated with water and injected with water, 10 mg/kg or 20 mg/kg fluoxetine. N’s per treatment of rats subchronically treated with 10 mg/kg fluoxetine were 7, 14 and 8. In 1B, data are the mean ± S.E. lordosis quality. N’s per treatment were 12, 7, and 7, respectively, for rats subchronically treated with water and injected with water, 10 mg/kg or 20 mg/kg fluoxetine. N’s per treatment of rat subchronically treated with 10 mg/kg fluoxetine were 7, 14 and 8. Single asterisks indicate a significant difference from the water-water control. The # symbol indicates a significant difference from the fluoxetine-water control. The double asterisk indicates a significant reduction in the effect of the acute fluoxetine treatment in rats previously injected with fluoxetine.
Figure 2
Figure 2. Fluoxetine effects in male preference testing
Ovariectomized rats were treated as described for Figure 1. Male preference testing took place immediately after lordosis testing. Data are the mean ± S.E. male preference ratios. N’s per treatment for rats subchronically treated with water and injected with water, 10 mg/kg fluoxetine or 20 mg/kg fluoxetine were 6, 5, and 8, respectively. For rats subchronically treated with 10 mg/kg fluoxetine, N’s were 5, 8, and 7.
Figure 3
Figure 3. Fluoxetine effects on crossings and grooming
Ovariectomized rats were treated as described for Figure 1. Male preference testing took place immediately after lordosis testing. Data are the mean ± S.E. number of times the female crossed the midline of the apparatus (3A) and seconds of grooming (3B). N’s per treatment for rats subchronically treated with water and injected with water, 10 mg/kg fluoxetine or 20 mg/kg fluoxetine were 6, 5, and 8, respectively. For rats subchronically treated with 10 mg/kg fluoxetine, N’s were 5, 8, and 7.
Figure 4
Figure 4. Fluoxetine effects on body weight
Data are the mean ± S.E. body weights for 31 rats subchronically injected with water and 34 rats subchronically treated with 10 mg/kg fluoxetine. Rats were ovariectomized 2 weeks before initiation of the experiment. Day 1 in the figure indicates body weight immediately prior to the first injection. The asterisk indicates the first day on which body weights of fluoxetine-treated rats were significantly lower than the water controls.
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