2. Academic Validation
  3. MK-801 attenuates one-trial tolerance in the elevated plus maze via the thalamic nucleus reuniens

MK-801 attenuates one-trial tolerance in the elevated plus maze via the thalamic nucleus reuniens

  • Neuropharmacology. 2025 May 1:268:110318. doi: 10.1016/j.neuropharm.2025.110318.
Xue Xu 1,  Qian Gong 2,  Xiao-Dong Wang 3
Affiliations

Affiliations

  • 1 Nanhu Brain-computer Interface Institute, Hangzhou, 311100, China; Lingang Laboratory, Shanghai, 200031, China. Electronic address: xux@zjbci.com.
  • 2 Department of Psychiatry of Sir Run Run Shaw Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, 310058, Hangzhou, China.
  • 3 Nanhu Brain-computer Interface Institute, Hangzhou, 311100, China; Department of Psychiatry of Sir Run Run Shaw Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, 310058, Hangzhou, China; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, 1369 West Wenyi Road, Hangzhou, 311121, China; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, 310058, China. Electronic address: xiaodongwang@zju.edu.cn.
PMID: 39842626 DOI: 10.1016/j.neuropharm.2025.110318
Abstract

Anxiety, a future-oriented negative emotional state, is characterized by heightened arousal and vigilance. The elevated plus maze (EPM) test is a widely used assay of anxiety-related behaviors in rodents and shows a phenomenon where Animals with prior test experience tend to avoid open arms in retest sessions. While this one-trial tolerance (OTT) phenomenon limits the reuse of the EPM test, the potential mechanisms remain unsolved. Here, we found that neither anxiogenic factors like acute restraint stress nor anxiolytic factors like diazepam (2 mg/kg) influenced the emergence of the OTT phenomenon in mice in the EPM test. In contrast, OTT was markedly attenuated by MK-801 (0.1 mg/kg), a non-competitive N-methyl-D-aspartate receptor antagonist. Through the use of c-Fos mapping, MK-801 was found to increase neuronal activation in the thalamic nucleus reuniens (Re). Moreover, chemogenetic inactivation of Re neurons could prevent the effects of MK-801. Our findings suggest the Re as a crucial brain region in emotional adaptation in the EPM and shed light on the experimental design optimization and mechanistic investigation of anxiety-related behaviors.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z