Ninjin'yoeito, a traditional Japanese Kampo medicine, suppresses the onset of anhedonia induced by dysfunction in the striatal dopamine receptor type 2-expressing medium spiny neurons.

Abstract

OBJECTIVE:

Recent studies have suggested that ninjin'yoeito (NYT), a traditional Japanese Kampo medicine, improves diminished motivation in humans and animals, rendering it a novel therapeutic option for impaired motivation. To better characterize the effect of NYT on motivation, we examined its effect on motivated behaviors in mice.

METHODS:

Mouse models of neurodegeneration-related apathy, in which striatal dopamine receptor type 2-expressing medium spiny neurons (D2-MSNs) were progressively damaged by diphtheria toxin expression, were chosen.

RESULTS:

The decrease in effort-based operant responding for rewards (sucrose pellets), indicative of the mouse's motivated behavior, in the affected mice was not suppressed by chronic treatment with NYT suspended in drinking water at 1% (w/v). Mice were then subjected to a sucrose preference test, wherein they freely chose to ingest tap water and a sucrose solution without being required to exert effort. The affected mice showed a decline in preference for sucrose over tap water, relative to nonaffected controls, indicating anhedonia-like traits. In contrast to the diminished operant behavior, the anhedonic behavior in the affected mice was prevented by the NYT administration. Furthermore, NYT did not affect the size of Drd2 mRNA disappearance in the striatum of affected mice, suggesting that the NYT effect was unrelated to DTA-mediated neurodegeneration.

CONCLUSION:

These results demonstrate that the beneficial effect of NYT on motivation is mediated, at least in part, through the potentiation of hedonic capacity by certain neuromodulatory pathways.

• Authors: Hiroaki Oizumi, Ryota Imai, Toru Suzuki, Yuji Omiya, Kenji F Tanaka, Masaru Mimura, Kazushige Mizoguchi
• Journal: Neuroreport (Neuroreport) Vol. 32 Issue 10 Pg. 869-874 (07 07 2021) ISSN: 1473-558X [Electronic] England
• PMID: 34029288 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Chemical References

• Drugs, Chinese Herbal
• Receptors, Dopamine D2
• ninjin'yoeito

Topics

• Anhedonia (drug effects, physiology)
• Animals
• Conditioning, Operant (drug effects, physiology)
• Corpus Striatum (drug effects, metabolism)
• Drugs, Chinese Herbal (pharmacology)
• Gene Expression
• Japan
• Medicine, Kampo (methods)
• Mice
• Mice, 129 Strain
• Mice, Inbred C57BL
• Mice, Inbred CBA
• Mice, Transgenic
• Motivation (drug effects, physiology)
• Neurons (drug effects, metabolism)
• Receptors, Dopamine D2 (biosynthesis, genetics)