Dopamine receptor agonist rotigotine-loaded microspheres ameliorates sexual function deteriorated by fluoxetine in depression rats

Abstract

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.