Kampo Research and Development Division, Tsumura & Co., Ibaraki, Japan.
Department of Bioregulation and Pharmacological Medicine, Fukushima Medical University School of Medicine, Fukushima, Japan.
Aging (Albany NY). 2022 Jun 3;14(11):4634-4652. doi: 10.18632/aging.204109.
The ventral tegmental area (VTA), substantia nigra pars compacta (SNpc) and nucleus accumbens (NAc) are involved in the regulation of appetite and motivational behaviors. A traditional Japanese (Kampo) medicine, ninjin'yoeito (NYT), has been reported to improve decreased motivation and anorexia in patients with Alzheimer's disease and apathy-like model mice. Thus, NYT may affect the activities of neurons in the VTA, SNpc and NAc. However, little is known about the underlying mechanisms of NYT. Here, we investigated the effects of NYT on the electrophysiological properties of dopaminergic neurons in the VTA and SNpc, as well as on those of medium spiny neurons (MSNs) in the NAc (core and shell subregions), by applying the patch-clamp technique in the brain slices. NYT reduced the resting membrane potential of VTA and SNpc dopaminergic neurons. In contrast, NYT increased the firing frequency of NAc MSNs accompanied by shortened first spike latency and interspike interval. Furthermore, NYT attenuated the inward rectification and sustained outward currents. In conclusion, NYT may directly influence the excitability of dopaminergic neurons in the VTA and SNpc, as well as MSNs in the NAc (core and shell). NYT may modulate dopamine signals in appetite and motivational behaviors.
腹侧被盖区（VTA）、黑质致密部（SNpc）和伏隔核（NAc）参与食欲和动机行为的调节。一种传统的日本（汉方）药物，人参叶提取物（NYT），据报道可改善阿尔茨海默病患者和类淡漠模型小鼠的动机减退和厌食症。因此，NYT 可能会影响 VTA、SNpc 和 NAc 神经元的活动。然而，关于 NYT 的潜在机制知之甚少。在这里，我们通过脑片应用膜片钳技术，研究了 NYT 对 VTA 和 SNpc 多巴胺能神经元以及 NAc（核心和壳区）中中间神经元（MSNs）电生理特性的影响。NYT 降低了 VTA 和 SNpc 多巴胺能神经元的静息膜电位。相反，NYT 增加了 NAc MSNs 的放电频率，同时缩短了第一峰潜伏期和峰间间隔。此外，NYT 减弱了内向整流和持续外向电流。总之，NYT 可能直接影响 VTA 和 SNpc 中的多巴胺能神经元以及 NAc（核心和壳）中的 MSNs 的兴奋性。NYT 可能调节食欲和动机行为中的多巴胺信号。
