Department of Neurobiology, Hebei Medical University, Shijiazhuang, China.
Central Laboratory, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
CNS Neurosci Ther. 2018 Feb;24(2):115-125. doi: 10.1111/cns.12781. Epub 2017 Dec 6.
Finasteride inhibits the conversion of testosterone to dihydrotestosterone. Because androgen regulates dopaminergic system in the brain, it could be hypothesized that finasteride may inhibit dopaminergic system. The present study therefore investigates the effects of finasteride in adolescent and early developmental rats on dopaminergic system, including contents of dopamine and its metabolites (dihydroxy phenyl acetic acid and homovanillic acid) and tyrosine hydroxylase expressions both at gene and protein levels. Meanwhile, open-field behaviors of the rats are examined because of the regulatory effect of dopaminergic system on the behaviors.
Open-field behaviors were evaluated by exploratory and motor behaviors. Dopamine and its metabolites were assayed by liquid chromatography-mass spectrometry. Tyrosine hydroxylase mRNA and protein expressions were determined by real-time qRT-PCR and western blot, respectively.
It was found that in adolescent male rats, administration of finasteride at doses of 25 and 50 mg/kg for 14 days dose dependently inhibited open-field behaviors, reduced contents of dopamine and its metabolites in frontal cortex, hippocampus, caudate putamen, nucleus accumbens, and down-regulated tyrosine hydroxylase mRNA and protein expressions in substantia nigra and ventral tegmental area. However, there was no significant change of these parameters in early developmental rats after finasteride treatment.
These results suggest that finasteride inhibits dopaminergic system and open-field behaviors in adolescent male rats by inhibiting the conversion of testosterone to dihydrotestosterone, and imply finasteride as a potential therapeutic option for neuropsychiatric disorders associated with hyperactivities of dopaminergic system and androgen.
非那雄胺抑制睾酮向二氢睾酮的转化。由于雄激素调节大脑中的多巴胺能系统，因此可以假设非那雄胺可能抑制多巴胺能系统。本研究因此调查了非那雄胺在青春期和早期发育期大鼠对多巴胺能系统的影响，包括多巴胺及其代谢物（二羟苯乙酸和高香草酸）的含量以及酪氨酸羟化酶在基因和蛋白水平上的表达。同时，由于多巴胺能系统对行为的调节作用，检查了大鼠的旷场行为。
通过探索性和运动行为评估旷场行为。通过液相色谱-质谱法测定多巴胺及其代谢物的含量。通过实时 qRT-PCR 和 Western blot 分别测定酪氨酸羟化酶 mRNA 和蛋白表达。
研究发现，在青春期雄性大鼠中，非那雄胺以 25 和 50mg/kg 的剂量连续给药 14 天，可剂量依赖性地抑制旷场行为，减少前额叶皮质、海马体、尾壳核、伏隔核和黑质中多巴胺及其代谢物的含量，并下调中脑腹侧被盖区和腹侧被盖区的酪氨酸羟化酶 mRNA 和蛋白表达。然而，非那雄胺处理后早期发育期大鼠的这些参数没有明显变化。
这些结果表明，非那雄胺通过抑制睾酮向二氢睾酮的转化抑制多巴胺能系统和青春期雄性大鼠的旷场行为，提示非那雄胺作为一种潜在的治疗选择，用于治疗与多巴胺能系统和雄激素过度活跃相关的神经精神障碍。
