Abstract：
BACKGROUND: Cabergoline (CAB) is an ergot derivative typically prescribed for the treatment of hyperprolactinemia. It suppresses the release of prolactin through agonist actions on dopamine (DA) D2 receptors; however, it possesses binding affinity for other DA and 5-HT receptors. Side effects that exacerbate valvular heart disease can occur with high doses.
OBJECTIVE: The present study examined the acute, subchronic, and chronic dose-response effects of CAB and a derivative dimethylcabergoline (DMC) which acts as an antagonist instead of agonist at 5-HT 2B receptors, on appetitive and consummatory sexual behaviors of male rats.
METHODS: CAB (0, 0.03, 0.15, or 0.3 mg/kg/ml) was administered daily to sexually experienced male rats (N = 10/dose) by oral gavage for a total of 68 days. Sexual behavior was tested every 4 days during this period for a total of 16 trials. On the 17th trial, rats were administered their dose of CAB, and 4 h after were overdosed with sodium pentobarbital, perfused intracardially, and their brains processed for Fos immunohistochemistry. DMC (0, 0.03, 0.15, 0.3 mg/kg/ml) was administered daily to sexually experienced male rats (N = 10/dose) by oral gavage for a total of 36 days. Sexual behavior was tested every 4 days for a total of 9 trials.
RESULTS: CAB increased anticipatory level changes, intromissions, and ejaculations significantly across all timepoints, with the medium and high doses being most potent. The medium and high doses also increased Fos protein significantly within the medial preoptic area, whereas in the nucleus accumbens shell, the low and medium doses decreased Fos protein but the high dose increased it significantly from control. Similar to CAB, the medium and high doses of DMC increased the number of ejaculations significantly. Rats in all drug dose groups appeared healthy for the duration of the experiments.
CONCLUSIONS: Both CAB and DMC facilitate ejaculations, and CAB further facilitates measures of anticipatory sexual motivation and intromissions. These data suggest that both could be used as treatments for sexual arousal disorders and ejaculation/orgasm disorders with little or no untoward side effects at low doses.
OBJECTIVE: The present study examined the acute, subchronic, and chronic dose-response effects of CAB and a derivative dimethylcabergoline (DMC) which acts as an antagonist instead of agonist at 5-HT 2B receptors, on appetitive and consummatory sexual behaviors of male rats.
METHODS: CAB (0, 0.03, 0.15, or 0.3 mg/kg/ml) was administered daily to sexually experienced male rats (N = 10/dose) by oral gavage for a total of 68 days. Sexual behavior was tested every 4 days during this period for a total of 16 trials. On the 17th trial, rats were administered their dose of CAB, and 4 h after were overdosed with sodium pentobarbital, perfused intracardially, and their brains processed for Fos immunohistochemistry. DMC (0, 0.03, 0.15, 0.3 mg/kg/ml) was administered daily to sexually experienced male rats (N = 10/dose) by oral gavage for a total of 36 days. Sexual behavior was tested every 4 days for a total of 9 trials.
RESULTS: CAB increased anticipatory level changes, intromissions, and ejaculations significantly across all timepoints, with the medium and high doses being most potent. The medium and high doses also increased Fos protein significantly within the medial preoptic area, whereas in the nucleus accumbens shell, the low and medium doses decreased Fos protein but the high dose increased it significantly from control. Similar to CAB, the medium and high doses of DMC increased the number of ejaculations significantly. Rats in all drug dose groups appeared healthy for the duration of the experiments.
CONCLUSIONS: Both CAB and DMC facilitate ejaculations, and CAB further facilitates measures of anticipatory sexual motivation and intromissions. These data suggest that both could be used as treatments for sexual arousal disorders and ejaculation/orgasm disorders with little or no untoward side effects at low doses.
摘要：
背景：卡麦角林（CAB）是一种麦角衍生物，通常用于治疗高催乳素血症。它通过对多巴胺（DA）D2受体的激动剂作用来抑制催乳素的释放；但是，它对其他DA和5-HT受体具有结合亲和力。高剂量可发生加重心脏瓣膜病的副作用。
目的：本研究检查了急性，亚慢性，以及CAB和衍生物二甲基卡麦角林（DMC）的慢性剂量反应效应，它在5-HT2B受体上充当拮抗剂而不是激动剂，雄性大鼠食欲和完善性行为的研究。
方法:通过口服管饲法对有性经历的雄性大鼠(N=10/剂)每日施用CAB(0、0.03、0.15或0.3mg/kg/ml),共68天。在此期间，每4天测试一次性行为，共进行16次试验。在第17次审判中,给大鼠服用剂量的CAB，和4小时后过量服用戊巴比妥钠，心内灌注,他们的大脑进行了Fos免疫组织化学处理。通过口服管饲法每天向有性经历的雄性大鼠（N=10/剂）施用DMC（0、0.03、0.15、0.3mg/kg/ml），共36天。每4天测试性行为，共9项试验。
结果：CAB增加了预期的水平变化，intromissions,在所有时间点都有明显的射精，中高剂量是最有效的。中等剂量和高剂量也显著增加了内侧视前区的Fos蛋白，而在伏隔核壳中，低剂量和中等剂量降低了Fos蛋白，但高剂量使其与对照组相比显着增加。类似于CAB,中、高剂量DMC显著增加射精次数。所有药物剂量组中的大鼠在实验期间表现为健康的。
结论：CAB和DMC都能促进射精，和CAB进一步促进了预期性动机和内省的措施。这些数据表明，两者都可以用作治疗性唤起障碍和射精/性高潮障碍，在低剂量下几乎没有或没有不良副作用。
目的：本研究检查了急性，亚慢性，以及CAB和衍生物二甲基卡麦角林（DMC）的慢性剂量反应效应，它在5-HT2B受体上充当拮抗剂而不是激动剂，雄性大鼠食欲和完善性行为的研究。
方法:通过口服管饲法对有性经历的雄性大鼠(N=10/剂)每日施用CAB(0、0.03、0.15或0.3mg/kg/ml),共68天。在此期间，每4天测试一次性行为，共进行16次试验。在第17次审判中,给大鼠服用剂量的CAB，和4小时后过量服用戊巴比妥钠，心内灌注,他们的大脑进行了Fos免疫组织化学处理。通过口服管饲法每天向有性经历的雄性大鼠（N=10/剂）施用DMC（0、0.03、0.15、0.3mg/kg/ml），共36天。每4天测试性行为，共9项试验。
结果：CAB增加了预期的水平变化，intromissions,在所有时间点都有明显的射精，中高剂量是最有效的。中等剂量和高剂量也显著增加了内侧视前区的Fos蛋白，而在伏隔核壳中，低剂量和中等剂量降低了Fos蛋白，但高剂量使其与对照组相比显着增加。类似于CAB,中、高剂量DMC显著增加射精次数。所有药物剂量组中的大鼠在实验期间表现为健康的。
结论：CAB和DMC都能促进射精，和CAB进一步促进了预期性动机和内省的措施。这些数据表明，两者都可以用作治疗性唤起障碍和射精/性高潮障碍，在低剂量下几乎没有或没有不良副作用。
