Finasteride, a 5α-Reductase inhibitor, is used to treat male pattern baldness and benign prostatic hyperplasia. Several clinical studies show that chronic finasteride treatment induces persistent depression, suicidal thoughts and cognitive impairment and these symptoms are persistent even after its withdrawal. Previous results from our lab showed that repeated administration of finasteride for six days induces depression-like behavior. However, whether short-term finasteride administration induces anxiety-like behavior and memory impairment and alters synaptic plasticity are not known, which formed the basis of this study. Finasteride was administered to 2–2.5 months old male Wistar rats for six days and subjected to behavioral evaluation, biochemical estimation and synaptic plasticity assessment. Anxiety-like behavior was evaluated in the elevated plus maze (EPM), open field test (OFT), light/dark test (LDT), and novelty suppressed feeding test (NSFT), and learning and memory using novel object recognition test (NORT) and novel object location test (NOLT) and depression-like behavior in the sucrose preference test (SPT). Synaptic plasticity in the hippocampal Schaffer collateral-CA1 was evaluated using slice field potential recordings. Plasma corticosterone levels were estimated using ELISA. Finasteride administration induced anxiety-like behavior in the EPM, OFT, LDT and NSFT, and depression-like behavior in the SPT. Further, finasteride induced hippocampal dependent spatial learning and memory impairment in the NOLT. In addition, finasteride decreased basal synaptic plasticity and long-term potentiation (LTP) in the hippocampus. A trend of increased plasma corticosterone levels was observed following repeated finasteride administration. These results indicate the potential role of corticosterone and synaptic plasticity in finasteride-induced effects and further studies will pave way for the development of novel neurosteroid-based therapeutics in neuropsychiatric diseases.

中文翻译：

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短期非那雄胺给药后的焦虑和抑郁样行为与雄性大鼠突触可塑性和认知行为受损有关


非那雄胺是一种 5α-还原酶抑制剂，用于治疗男性型脱发和良性前列腺增生。多项临床研究表明，长期非那雄胺治疗会导致持续的抑郁、自杀念头和认知障碍，并且这些症状即使在停药后也持续存在。我们实验室之前的结果表明，重复服用非那雄胺六天会诱发抑郁症样行为。然而，短期非那雄胺给药是否会引起焦虑样行为和记忆障碍以及改变突触可塑性尚不清楚，这构成了本研究的基础。将非那雄胺给予2-2.5个月大的雄性Wistar大鼠六天，并进行行为评估、生化评估和突触可塑性评估。通过高架十字迷宫（EPM）、旷场测试（OFT）、明/暗测试（LDT）和新奇抑制进食测试（NSFT）以及使用新物体识别测试（NORT）的学习和记忆来评估焦虑样行为）和新物体定位测试（NOLT）以及蔗糖偏好测试（SPT）中的抑郁样行为。使用切片场电位记录评估海马 Schaffer 侧支 CA1 的突触可塑性。使用 ELISA 估计血浆皮质酮水平。非那雄胺给药诱导 EPM、OFT、LDT 和 NSFT 中的焦虑样行为，以及 SPT 中的抑郁样行为。此外，非那雄胺在 NOLT 中诱导海马依赖性空间学习和记忆障碍。此外，非那雄胺降低了海马的基础突触可塑性和长时程增强（LTP）。重复服用非那雄胺后观察到血浆皮质酮水平增加的趋势。 这些结果表明皮质酮和突触可塑性在非那雄胺诱导的效应中的潜在作用，进一步的研究将为开发基于神经类固醇的新型神经精神疾病疗法铺平道路。