Comparison of female Fischer and Sprague-Dawley rats in the response to ketanserin

Abstract

The effects of the 5-HT2A/2C receptor antagonist, ketanserin, on lordosis behavior were examined in hormonally primed, ovariectomized Fischer and Sprague-Dawley females. Rats were primed with 0.067μg/g body weight estradiol benzoate and 3.33μg/g body weight progesterone. After a pretest for sexual behavior, rats were injected with 0.416 to 10mg/kg ketanserin. In both strains, lordosis behavior, lordosis quality, and proceptivity were significantly reduced by ketanserin. There was modest evidence of a strain difference with Sprague-Dawley females slightly more sensitive to ketanserin. In a second experiment, the effects of 10mg/kg fluoxetine, 1mg/kg ketanserin, and their combination were examined to determine if the two drugs would have additive effects on sexual behavior. There was no evidence that the drugs were additive in their effect and the strains did not differ in their response to the combined treatment. These findings are discussed in relation to prior evidence for strain differences in the sexual behavioral response to fluoxetine and to a receptor agonist acting preferentially at 5-HT1A receptors.

Keywords: 5-HT(2) receptors; Fluoxetine; Lordosis behavior; Ovariectomized; Proceptivity; Rat strains.

Figure 1. L/M ratio after varying doses of ketanserin treatment

Hormonally primed, ovariectomized rats were pretested for sexual behavior 4 to 6 hr after progesterone. Rats were then injected with deionized (DI) water or with 0.416, 0.5, 0.75, 1, 2, 5 or 10 mg/kg of ketanserin. Fifteen minutes later, rats were again tested for two consecutive 15 min intervals. Data are the mean ± SE L/M ratios for the two 15 min interval after injection with deionized water or ketanserin. Pretest L/M ratios (0.99 ± 0.003 and 0.98 ± 0.007, respectively, for Fischer and Sprague-Dawley females) did not differ between strains. The Ns for Fischer rats for (DI) water or 0.416, 0.5, 0.75, 1, 2, 5 or 10 mg/kg of ketanserin, respectively, were 5, 8, 9, 6, 10, 5, 13 and 7. Ns for Sprague-Dawley rats, respectively, were 5, 8, 10, 6, 9, 5, 14 and 6. *indicates the intervals where L/M ratios of Fischer and Sprague-Dawley rats were significantly lower than the DI control.

Figure 2. Lordosis quality after ketanserin treatment

Data are the mean ± SE lordosis quality score for the pretest and two 15 intervals after treatment with ketanserin or deionized water (DI) and are for the same rats as in Figure 1. The Ns for Fischer rats for DI water or 0.416, 0.5, 0.75, 1, 2, 5 or 10 mg/kg of ketanserin, respectively, were 5, 8, 9, 6, 10, 5, 13 and 7. Ns for Sprague-Dawley rats, respectively, were 5, 8, 10, 6, 9, 5, 14 and 6. *indicates the intervals where lordosis quality of Fischer and Sprague-Dawley rats were significantly lower than the DI control.

Figure 3. Effects of ketanserin on proceptivity

Data are the percentage of rats showing proceptivity after the various doses of ketanserin treatment and for the same rats as in Figure 1. The inset shows the percentage of rats when collapsed across doses of ketanserin. *indicates significant decline in proceptivity relative to the DI control, within strain.

Figure 4. Ketanserin and fluoxetine are not additive for lordosis inhibition

Hormonally primed, ovariectomized rats were pretested for sexual behavior 4 to 6 hr after progesterone. Rats were then injected with 10 mg/kg fluoxetine or deionized water (DI). Fifteen minutes later DI injected rats were injected with 1 mg/kg ketanserin; fluoxetine-treated rats were injected with 1 mg/kg ketanserin or DI. This led to three groups, fluoxetine only, ketanserin only, fluoxetine and ketanserin. Fifteen minutes later, rats were again tested for 15 consecutive min. Data are the mean ± SE L/M ratios for the pretest and 15 consecutive min after injection. The Ns for Fischer rats given fluoxetine, ketanserin, or both drugs were 8, 7 and 11. Ns for Sprague-Dawley rats given fluoxetine, ketanserin, or both drugs were 7, 7 and 11. *indicates significant difference from the pretest within treatment, # indicates a difference from fluoxetine within strain.

Figure 5. Effects of fluoxetine, ketanserin, and their combination on proceptivity

Data are the percentage of rats showing proceptivity after the 3 treatments and are for the same rats as in Figure 4. Data are for the Pretest and the 15 min interval after treatment. *indicates a significant difference from the pretest and fluoxetine, within strain.