重复服用非那雄胺可促进突触可塑性,并对雌性大鼠产生抗抑郁和抗焦虑作用。

IF 2.9 3区 医学 Q2 NEUROSCIENCES
Jose Nayana, Byrathnahalli S. Shankaranarayana Rao, Bettadapura N. Srikumar
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引用次数: 0

摘要

非那雄胺用于治疗女性脱发、多毛症和多囊卵巢综合症。它能抑制 5α 还原酶,而 5α 还原酶是神经类固醇生物合成过程中的一种重要酶。非那雄胺治疗对女性患者精神健康的影响,以及对雌性啮齿类动物反复/长期服用非那雄胺的影响尚不清楚。因此,在我们的研究中,我们对雌性大鼠连续6天施用非那雄胺(10、30或100毫克/千克,静脉注射),并对其行为、血浆类固醇水平和突触可塑性进行了评估。通过强迫游泳试验(FST)和飞溅试验评估抑郁样行为。焦虑样行为通过新奇抑制喂食任务(NSFT)、高架加迷宫(EPM)、空场试验(OFT)和光-暗试验(LDT)进行评估。血浆类固醇水平采用酶联免疫吸附法进行评估,突触可塑性采用场电位记录法进行评估。我们观察到,非那雄胺减少了FST的总静止持续时间,显示了抗抑郁样作用;减少了NSFT的首次咬合潜伏期,显示了抗焦虑样作用。我们还发现血浆雌二醇水平明显升高,血浆皮质酮水平明显降低。此外,场电位记录显示非那雄胺可增加海马的长期电位。这些结果表明,雌性大鼠反复服用非那雄胺可能具有类似抗抑郁和抗焦虑的作用,而这种作用可能是通过提高雌二醇水平或降低皮质酮水平来实现的。要验证非那雄胺对雌性大鼠影响的分子机制,还需要进一步的研究。了解这些机制将有助于我们开发基于神经类固醇的新型疗法,用于治疗女性神经精神疾病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Repeated finasteride administration promotes synaptic plasticity and produces antidepressant- and anxiolytic-like effects in female rats

Repeated finasteride administration promotes synaptic plasticity and produces antidepressant- and anxiolytic-like effects in female rats

Finasteride is used in female-pattern hair loss, hirsutism, and polycystic ovarian syndrome. It inhibits 5α-reductase, which is an important enzyme in the biosynthesis of neurosteroids. The effects of finasteride treatment on mental health in female patients as well as the effects of repeated/chronic finasteride administration in female rodents are still unknown. Accordingly, in our study, we administered finasteride (10, 30, or 100 mg/Kg, s.c.) for 6 days in female rats and evaluated behavior, plasma steroid levels, and synaptic plasticity. Depression-like behavior was evaluated using forced swim test (FST) and splash test. Anxiety-like behavior was evaluated using novelty-suppressed feeding task (NSFT), elevated plus maze (EPM), open field test (OFT), and light–dark test (LDT). Plasma steroid levels were assessed using ELISA and synaptic plasticity by field potential recordings. We observed that finasteride decreased total immobility duration in FST, indicating antidepressant-like effect and decreased the latency to first bite in NSFT, showing anxiolytic-like effect. We also found a significant increase in plasma estradiol and a significant decrease in plasma corticosterone level. Furthermore, field potential recordings showed that finasteride increased hippocampal long-term potentiation. These results indicate that repeated finasteride administration in female rats may have antidepressant- and anxiolytic-like effect, which might be mediated by enhanced estradiol levels or decreased corticosterone levels. Further studies are required to validate the molecular mechanisms underlying the effects of finasteride in female rats. Understanding the mechanisms will help us in developing novel neurosteroid-based therapeutics in the treatment of neuropsychiatric disorders in women.

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来源期刊
Journal of Neuroscience Research
Journal of Neuroscience Research 医学-神经科学
CiteScore
9.50
自引率
2.40%
发文量
145
审稿时长
1 months
期刊介绍: The Journal of Neuroscience Research (JNR) publishes novel research results that will advance our understanding of the development, function and pathophysiology of the nervous system, using molecular, cellular, systems, and translational approaches. JNR covers both basic research and clinical aspects of neurology, neuropathology, psychiatry or psychology. The journal focuses on uncovering the intricacies of brain structure and function. Research published in JNR covers all species from invertebrates to humans, and the reports inform the readers about the function and organization of the nervous system, with emphasis on how disease modifies the function and organization.
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