School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, 12682Yantai University, Yantai, Shandong 264005, PR China.
ASN Neuro. 2021 Jan-Dec;13:17590914211052862. doi: 10.1177/17590914211052862.
Low dopamine levels may cause depressive symptoms. Dopamine is also involved in sexual behavior. Rotigotine is a nonergolinic dopamine agonist. Fluoxetine, an antidepressant that acts as a selective serotonin (5-HT) reuptake inhibitor, may cause moderate or severe sexual dysfunction. This study aims to investigate the effects of rotigotine-loaded microspheres (RoMS) and rotigotine on fluoxetine-induced impairment of sexual function and their efficacy in depression-model rats. Rats with depressive-like behavior, induced by bilateral olfactory bulbectomy, were treated intragastrically with fluoxetine and co-administered RoMS or rotigotine subcutaneously. Then, copulatory behavior and open field tests were conducted. Serum luteinizing hormone and testosterone levels were assayed with enzyme-linked immunosorbent assay kits. The concentrations of 5-HT, dopamine, and norepinephrine were measured in the raphe nucleus and amygdala. The results showed that sexual function was decreased in olfactory bulbectomy rats and significantly deteriorated by fluoxetine. Co-administration of RoMS partly reversed the fluoxetine-induced impairment of sexual function, but rotigotine administration did not produce any improvement. Hyperactivity in olfactory bulbectomy rats was significantly attenuated by fluoxetine but was not influenced by co-administration of RoMS. Compared with the fluoxetine group, RoMS increased the testosterone, luteinizing hormone, dopamine, and norepinephrine levels. These findings indicated that RoMS improved the fluoxetine-induced impairment of sexual function and did not affect its antidepressant efficacy in depressive rats, which provides a potential treatment for patients with depression that can reduce the possibility of sexual dysfunction. Additionally, co-administration of fluoxetine with RoMS may be beneficial for Parkinson's disease patients with depression.
多巴胺水平降低可能导致抑郁症状。多巴胺也参与性行为。罗替高汀是一种非麦角灵的多巴胺激动剂。氟西汀是一种作为选择性 5-羟色胺（5-HT）再摄取抑制剂的抗抑郁药，可能导致中度或重度性功能障碍。本研究旨在探讨载罗替高汀微球（RoMS）和罗替高汀对氟西汀引起的性功能障碍的影响及其在抑郁模型大鼠中的疗效。通过双侧嗅球切除术诱导具有抑郁样行为的大鼠，通过胃内给予氟西汀和皮下给予 RoMS 或罗替高汀进行治疗。然后进行交配行为和旷场试验。用酶联免疫吸附试剂盒测定血清黄体生成素和睾酮水平。测量中缝核和杏仁核中 5-HT、多巴胺和去甲肾上腺素的浓度。结果表明，嗅觉球切除术大鼠的性功能下降，氟西汀显著恶化。RoMS 的共同给药部分逆转了氟西汀引起的性功能障碍，但罗替高汀给药没有产生任何改善。氟西汀显著减轻嗅球切除术大鼠的过度活动，但 RoMS 的共同给药没有影响。与氟西汀组相比，RoMS 增加了睾酮、黄体生成素、多巴胺和去甲肾上腺素水平。这些发现表明，RoMS 改善了氟西汀引起的性功能障碍，而不会影响其在抑郁大鼠中的抗抑郁疗效，为患有抑郁症的患者提供了一种潜在的治疗方法，可以降低性功能障碍的可能性。此外，氟西汀与 RoMS 联合给药可能对患有抑郁症的帕金森病患者有益。
