Facilitation of sexual behavior in ovariectomized rats by estradiol and testosterone: A preclinical model of androgen effects on female sexual desire

摘要

In the United States and Canada, there are no approved treatments for hypoactive sexual desire disorder in postmenopausal women. Testosterone improves female sexual desire in naturally- and surgically menopausal women maintained on estrogen replacement therapy, and long-term safety data from randomized placebo-controlled clinical trials has yielded promising results. However, the mechanisms associated with its efficacy are not known, and could be addressed using preclinical rodent models; yet there is no systematic evaluation of the effects of estradiol and testosterone on female rat sexual behavior. The aim of these studies was to assess whether testosterone propionate (TP) facilitates sexual behaviors, particularly appetitive sexual behaviors, in Long-Evans and Wistar ovariectomized (OVX) rats primed with estradiol benzoate (EB). In Experiment 1, Long-Evans OVX rats were treated with Oil (0), 10 mu g EB + O, O + 200 mu g TP, 10 mu g EB + 500 mu g progesterone (P), or 10 mu g EB + 200 mu g TP. In Experiment 2a, Wistar OVX rats were treated with varying doses of EB (2.5, 5, or 10 mu g) 48h prior, and TP (0, 200, or 400 mu g) 4h prior to testing in a Latin-Square design. A subset of animals was used in Experiment 2b and treated sequentially with EB (0, 2.5, 5, or 10 mu g) followed by TP (0, 200, or 400 mu g, in a Latin-Square design) 48 h prior to sexual behavior testing. All tests occurred in the bilevel pacing chamber. Frequencies of female appetitive (hops/darts, solicitations, level changes) and consummatory (lordosis quotient and magnitude) sexual behaviors as well as the number of defensive behaviors towards males were scored. Number of mounts, intromissions and ejaculations from males were also scored. In EB-primed OVX Long Evans rats, 200 mu g TP administered 4h prior to testing facilitated hops/darts and lordosis ratings beyond EB alone, and to levels equivalent to EB + P. In contrast, that regimen was not successful in EB-primed OVX Wistar rats. When EB and TP were co-administered 48 h prior to testing, 10 mu g EB + 200 mu g TP significantly increased hops/darts and level changes beyond that observed by 10 mu g EB alone. In summary, the administration of EB and TP to OVX Long-Evans and Wistar rats facilitates appetitive measures of sexual behavior. Strain differences exist that likely reflect underlying differences in sensitivities to EB, and the EB-primed OVX Long-Evans rat may be useful for studying mechanisms of TP-facilitation of desire due to higher baseline sexual inhibition. (C) 2017 Elsevier Ltd. All rights reserved.