Department of Biology, Texas Woman's University, Denton, TX 76204, USA.
J Sex Med. 2013 Feb;10(2):350-61. doi: 10.1111/j.1743-6109.2012.02981.x. Epub 2012 Oct 30.
The selective serotonin reuptake inhibitor (SSRI), fluoxetine, leads to sexual dysfunction in a substantial proportion of women. In studies with the Fischer inbred rat, the 5-HT(1A) receptor has been implicated in this sexual dysfunction. Whether this association with 5-HT(1A) receptors holds for other rat strains is not known.
The effects of acute fluoxetine on sexual behavior in two strains of rats that differ in their response to a 5-HT(1A) receptor agonist were examined. Whether the strain difference is comparable in naturally cycling and hormonally primed, ovariectomized rats was determined.
Proestrous rats and ovariectomized rats, hormonally primed with estradiol benzoate and progesterone, were treated with varying doses of fluoxetine. Sexual behavior was examined before and after treatment with the SSRI.
Lordosis to mount ratios, lordosis quality, and proceptive behaviors were quantified. Sprague-Dawley and Fischer females were compared on each of these measures. The IC(50) for inhibition of lordosis behavior was determined.
In both the intact and the hormonally primed, ovariectomized model, Sprague-Dawley females were less sensitive to the effects of fluoxetine on sexual behavior. In both groups, fluoxetine showed dose dependency in behavioral inhibition, but a higher dose was required for Sprague-Dawley than for Fischer females. Naturally cycling, proestrous rats required a higher dose of fluoxetine than hormonally primed ovariectomized rats to produce significant inhibition of sexual behavior. Thus, the strain difference in the response to fluoxetine does not parallel strain differences in the response to a 5-HT(1A) receptor agonist.
Acute treatment with fluoxetine inhibits lordosis behavior in both Fischer and Sprague-Dawley females and the strain difference cannot be explained by reported strain differences in the response to a 5-HT(1A) receptor agonist. Fluoxetine's inhibition of female rat sexual behavior may involve effects of the SSRI in addition to activation of the 5-HT(1A) receptor.
选择性 5-羟色胺再摄取抑制剂（SSRI）氟西汀会导致相当一部分女性出现性功能障碍。在对 Fischer 近交系大鼠的研究中，5-HT（1A）受体被认为与这种性功能障碍有关。但这种与 5-HT（1A）受体的关联是否适用于其他大鼠品系尚不清楚。
本研究旨在检测两种对 5-HT（1A）受体激动剂反应不同的大鼠品系中，氟西汀急性给药对性行为的影响。同时还确定了自然发情和激素诱导去卵巢大鼠中这种品系差异是否具有可比性。
对发情前期大鼠和用苯甲酸雌二醇和孕酮激素诱导的去卵巢大鼠进行不同剂量的氟西汀处理。用 SSRI 治疗前后，检测性行为。
记录交配体位比、交配体位质量和求爱行为，并对这些指标进行量化。比较 Sprague-Dawley 和 Fischer 雌性大鼠的这些指标。同时还确定了抑制发情行为的 IC（50）值。
在完整和激素诱导去卵巢模型中，Sprague-Dawley 雌性大鼠对氟西汀对性行为的影响的敏感性较低。在两组中，氟西汀对行为抑制具有剂量依赖性，但 Sprague-Dawley 大鼠所需的剂量高于 Fischer 大鼠。与激素诱导去卵巢大鼠相比，自然发情的发情前期大鼠需要更高剂量的氟西汀才能显著抑制性行为。因此，对氟西汀的反应的品系差异与对 5-HT（1A）受体激动剂的反应的品系差异并不平行。
急性给予氟西汀可抑制 Fischer 和 Sprague-Dawley 雌性大鼠的交配体位行为，且这种品系差异不能用报道的对 5-HT（1A）受体激动剂的反应的品系差异来解释。氟西汀抑制雌性大鼠性行为可能除了激活 5-HT（1A）受体外，还涉及 SSRI 的其他作用。
