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Advances in chemogenetics: a review of DREADDs and its application in psychiatric disorders

Molecular Psychiatry volume 31, pages 480–497 (2026) Cite this article

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Abstract

Chemogenetics is a rapidly advancing field that uses genetically engineered receptors to selectively modulate the activity of specific neuronal populations in the brain. This innovative approach allows for precise control of neural circuits, providing valuable insights into the roles of specific circuits in behavior and disease mechanisms. The potential of chemogenetics to transform our understanding of brain function could lead to novel therapeutic strategies for a wide range of neurological and psychiatric disorders. This review explores the fundamental mechanisms of chemogenetics, with a focus on Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) and their associated ligands. We provide a comprehensive overview of the various classes of DREADDs, detailing optimal ligand dosing and offering guidance for their integration into both research and clinical settings. Additionally, we examine the recent applications of DREADDs in psychiatry, particularly about brain regions and circuits involved in anxiety.

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Fig. 1: Milestones in the development and application of chemogenetics.
The alternative text for this image may have been generated using AI.
Fig. 2: Mechanisms and downstream pathways of various DREADDs.
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Fig. 3: In vivo administration of ligands targeting DREADDs.
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Fig. 4: Application of chemogenetics in neuroscience.
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Fig. 5: Application of DREADDs in psychiatric disorders.
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Fig. 6: Chemogenetic regulation in the treatment of stress-induced anxiety.
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Acknowledgements

This work was supported by the National Natural Science Foundation of China (82471536, 32500517); Department of Science and Technology of Zhejiang Province (2023ZY1018, 2024SSYS0054); Wenzhou Science and Technology Projects (ZY2023006, 2024R2002); and Oujiang Laboratory (OJQD2022002, OJQDJQ2022002).

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Authors and Affiliations

  1. Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Institute of Aging, Key Laboratory of Alzheimer’s Disease of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, P.R. China

    Jingyao Gao, Tong Ye, Xingwang Chen, Jie Yang, Shumin Wu, Wei Wang, Zhipei Liu, Li Huang, Weihong Song & Tao Tan

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  1. Jingyao Gao
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  2. Tong Ye
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  6. Wei Wang
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Contributions

J.G. conducted the literature search and drafted the paper. T.Y., X.C., J.Y., S.W., W.W., Z.L., and L.H. wrote part of the paper. T.T. designed the outline of the review, supervised the entire process. T.T. and W.S. revised the paper.

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Correspondence to Weihong Song or Tao Tan.

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Gao, J., Ye, T., Chen, X. et al. Advances in chemogenetics: a review of DREADDs and its application in psychiatric disorders. Mol Psychiatry 31, 480–497 (2026). https://doi.org/10.1038/s41380-025-03305-5

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