Neural circuits for stress-induced water drinking in relief of anxiety

L Lan Tang (Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Center for Advance Interdisciplinary Science and Biomedicine of Institute of Health and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China) R Run-Jie Wu (Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Center for Advance Interdisciplinary Science and Biomedicine of Institute of Health and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China) H Hong-Yu Li (Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Center for Advance Interdisciplinary Science and Biomedicine of Institute of Health and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China) H Hong-Rui Wei (Division of Life Sciences and Medicine, University of Science and Technology of China) J Jing-Bo Duan (Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Center for Advance Interdisciplinary Science and Biomedicine of Institute of Health and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China) Q Qianqian Lou (Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China) L Le-Xian Li (Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Center for Advance Interdisciplinary Science and Biomedicine of Institute of Health and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China) X Xin-Lu Yang (Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China) W Wei Gao M Min Zhu Z Zhi Zhang S Sen Qun (Department of Neurology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China) Y Yuanzhong Kai (Department of Biopharmaceuticals, School of Life Sciences and Medical Engineering, Anhui University) Y Yan Jin

Abstract

Drinking water is a rapid, instinctive behavior of mammals following stress. The role of such stress-induced water drinking behavior and its neural mechanisms remain poorly known. Here, we identify two sequentially activated neural circuits that respectively mediate stress-induced drinking behavior and reward encoding, which collectively promote the extinction of anxiety-like behaviors in mice. Specifically, mild short-term stress induces anxiety-like behaviors and activates glutamatergic neurons in the medial prefrontal cortex (mPFC Glu ) projecting to glutamatergic neurons in the median preoptic nucleus (MnPO Glu ), consequently driving drinking behavior in mice. This drinking behavior subsequently activates GABAergic neurons in the MnPO (MnPO GABA ), which then inhibit GABAergic neurons in the ventral tegmental area (VTA GABA ), leading to disinhibition of reward-encoding dopaminergic VTA neurons (VTA DA ), ultimately mediating the extinction of stress-induced anxiety-like behaviors. The present study defines cortical–hypothalamic–midbrain connections underlying the anxiety-relieving effects of drinking behavior, providing a circuit basis for innate stress coping strategies.

Article Details

Volume / Issue Vol. 123, Issue 29
Published July 21, 2026
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (14)

L

Lan Tang

Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Center for Advance Interdisciplinary Science and Biomedicine of Institute of Health and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China

R

Run-Jie Wu

Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Center for Advance Interdisciplinary Science and Biomedicine of Institute of Health and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China

H

Hong-Yu Li

Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Center for Advance Interdisciplinary Science and Biomedicine of Institute of Health and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China

H

Hong-Rui Wei

Division of Life Sciences and Medicine, University of Science and Technology of China

J

Jing-Bo Duan

Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Center for Advance Interdisciplinary Science and Biomedicine of Institute of Health and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China

Q

Qianqian Lou

Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China

L

Le-Xian Li

Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Center for Advance Interdisciplinary Science and Biomedicine of Institute of Health and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China

X

Xin-Lu Yang

Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China

W

Wei Gao

M

Min Zhu

Z

Zhi Zhang

S

Sen Qun

Department of Neurology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China

Y

Yuanzhong Kai

Department of Biopharmaceuticals, School of Life Sciences and Medical Engineering, Anhui University

Y

Yan Jin