Research Paper Volume 14, Issue 11 pp 4634—4652

The effects of ninjin’yoeito on the electrophysiological properties of dopamine neurons in the ventral tegmental area/substantia nigra pars compacta and medium spiny neurons in the nucleus accumbens

Ryota Imai1,2, , Keita Mizuno1, , Yuji Omiya1, , Kazushige Mizoguchi1, , Yuko Maejima2, , Kenju Shimomura2, ,

  • 1 Kampo Research and Development Division, Tsumura & Co., Ibaraki, Japan
  • 2 Department of Bioregulation and Pharmacological Medicine, Fukushima Medical University School of Medicine, Fukushima, Japan

Received: November 27, 2021       Accepted: May 23, 2022       Published: June 3, 2022
How to Cite

Copyright: © 2022 Imai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


VTA: ventral tegmental area; SNpc: substantia nigra pars compacta; NAc: nucleus accumbens; PFC: prefrontal cortex; DA: dopamine; MSN: medium spiny neuron; NYT: ninjin’yoeito; AD: Alzheimer’s disease; DAT: dopamine transporter; TH-GFP: tyrosine hydroxylase green fluorescence protein; RMP: resting membrane potential; ISI: interspike interval; I-V: current-voltage; CsCl: cesium chloride; IPSC: inhibitory postsynaptic current; aCSF: artificial cerebrospinal fluid; DMSO: dimethyl sulfoxide; CNQX: 6-cyano-7-nitroquinoxaline-2,3-dione disodium salt; AP5: D-(−)-2-amino-5-phosphonopentanoic acid.