Islam Md Nabiul, Sakimoto Yuya, Jahan Mir Rubayet, Miyasato Emi, Tarif Abu Md Mamun, Nozaki Kanako, Masumoto Koh-Hei, Yanai Akie, Mitsushima Dai, Shinoda Koh
Division of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan.
Department of Physiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan.
Brain Sci. 2021 Feb 14;11(2):239. doi: 10.3390/brainsci11020239.
Adolescence is the critical postnatal stage for the action of androgen in multiple brain regions. Androgens can regulate the learning/memory functions in the brain. It is known that the inhibitory avoidance test can evaluate emotional memory and is believed to be dependent largely on the amygdala and hippocampus. However, the effects of androgen on inhibitory avoidance memory have never been reported in adolescent male rats. In the present study, the effects of androgen on inhibitory avoidance memory and on androgen receptor (AR)-immunoreactivity in the amygdala and hippocampus were studied using behavioral analysis, Western blotting and immunohistochemistry in sham-operated, orchiectomized, orchiectomized + testosterone or orchiectomized + dihydrotestosterone-administered male adolescent rats. Orchiectomized rats showed significantly reduced time spent in the illuminated box after 30 min (test 1) or 24 h (test 2) of electrical foot-shock (training) and reduced AR-immunoreactivity in amygdala/hippocampal cornu Ammonis (CA1) in comparison to those in sham-operated rats. Treatment of orchiectomized rats with either non-aromatizable dihydrotestosterone or aromatizable testosterone were successfully reinstated these effects. Application of flutamide (AR-antagonist) in intact adolescent rats exhibited identical changes to those in orchiectomized rats. These suggest that androgens enhance the inhibitory avoidance memory plausibly by binding with AR in the amygdala and hippocampus.
青春期是雄激素在多个脑区发挥作用的关键产后阶段。雄激素可调节大脑中的学习/记忆功能。众所周知，抑制性回避试验可评估情绪记忆，且据信很大程度上依赖于杏仁核和海马体。然而，雄激素对青春期雄性大鼠抑制性回避记忆的影响尚未见报道。在本研究中，利用行为分析、蛋白质免疫印迹法和免疫组织化学，对假手术、去势、去势+睾酮或去势+双氢睾酮处理的雄性青春期大鼠进行研究，探讨雄激素对抑制性回避记忆以及杏仁核和海马体中雄激素受体（AR）免疫反应性的影响。与假手术大鼠相比，去势大鼠在电足电击（训练）30分钟（测试1）或24小时（测试2）后，在光照箱中停留的时间显著减少，杏仁核/海马体海马角（CA1）中的AR免疫反应性降低。用不可芳香化的双氢睾酮或可芳香化的睾酮对去势大鼠进行治疗，成功恢复了这些效应。在完整的青春期大鼠中应用氟他胺（AR拮抗剂）表现出与去势大鼠相同的变化。这些结果表明，雄激素可能通过与杏仁核和海马体中的AR结合来增强抑制性回避记忆。
