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. 2008 Dec 15:1245:52-60.
doi: 10.1016/j.brainres.2008.09.063. Epub 2008 Oct 2.

Modest effects of repeated fluoxetine on estrous cyclicity and sexual behavior in Sprague Dawley female rats

Navin Maswood  1 , Jhimly Sarkar, Lynda Uphouse
Affiliations

Modest effects of repeated fluoxetine on estrous cyclicity and sexual behavior in Sprague Dawley female rats

Navin Maswood et al. Brain Res. .

Abstract

In an earlier study, we reported that daily fluoxetine treatment (10 mg/kg/day) rapidly disrupted estrous cyclicity and sexual receptivity in adult, regularly cycling Fischer rats. The current study was designed to investigate if comparable fluoxetine treatment would similarly affect intact, regularly cycling Sprague Dawley rats. In the first experiment, fluoxetine was injected for 24 days. After 11-14 days of daily fluoxetine treatment, 40% of the rats showed a transient disturbance of the estrous cycle with elimination of sexual receptivity. In these affected rats, reduced sexual receptivity generally preceded disruption of vaginal cyclicity. In a second experiment, a shorter exposure was used to attempt to dissociate effects of fluoxetine on behavior and estrous cyclicity. Nine days of fluoxetine treatment eliminated sexual receptivity and proceptivity (hops/darts) in 40% and 46%, respectively, of rats without altering the estrous cycle. Female rats then received a 10th fluoxetine injection 30 min prior to assessment of sexual motivation (measured with the male preference paradigm). There was no effect of fluoxetine on male preference, but fluoxetine significantly reduced the number of crossings and seconds of grooming during preference testing. Therefore, effects of fluoxetine on estrous cyclicity and behavior of Sprague Dawley female rats were smaller and required longer to develop than previously reported in Fischer female rats. These findings reinforce a probable relationship between fluoxetine's effect on sexual activity and neuroendocrine disturbances and illustrate the importance of strain selection in attempting to model human disease.

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Figures

Figure 1
Figure 1. Percentage of female Sprague Dawley rats showing a proestrous smear after daily fluoxetine treatment
Intact, regularly cycling Sprague Dawley female rats were injected with 10 mg/kg fluoxetine (1 ml/kg) or an equivalent volume of distilled water beginning at diestrus 1 and continuing for 24 days. Data are the percentage of rats showing a proestrous smear in each of the treatment groups. Data were grouped into 5-days intervals for presentation. Control animals showed regular cyclicity throughout the experiment. In contrast, 6 out of 15 fluoxetine-treated rats showed an elongated cycle at least once during the experiment.
Figure 2
Figure 2. Percentage of female Sprague Dawley rats showing sexual receptivity during daily fluoxetine treatment
Data are for the same fluoxetine-treated females shown in Figure 1. Data are the percentage of females that showed sexual receptivity coincident with a proestrous smear. N’s for each of the 5-day intervals after injection with fluoxetine are 12, 12, 10, 12, and 12, respectively, but do not necessarily include the same set of animals during each 5-day interval.
Figure 3
Figure 3. Body weight and food intake of female Sprague Dawley rats during daily treatment with fluoxetine
Intact, regularly cycling female rats were injected daily with 10 mg/kg fluoxetine (1 ml/kg) or an equivalent volume of distilled/deionized water. Day 0 indicates body weight the day before the first injection; day 1 is the first day of injection. Body weight is shown in 3A and food intake is shown in 3B. Data are the mean ± S.E. body weight or food intake (in grams) for 15 fluoxetine and 15 control rats for each indicated day. In 3B, errors were so small that they are not always visible on the graph. On day 23–24, data are for 12 fluoxetine and 13 control rats. Since body weight was measured prior to injection, body weight is shown for one day more than is shown for food intake. The single asterisk indicates days on which there was a significant decrease in body weight or food intake in the fluoxetine-treated rats relative to their starting weight.
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