Evidence map›Paper›PMID 40702536›Full record

ArticleBehavioral and brain functions : BBF2025

Role of astrocytic mu-opioid receptors of the ventrolateral periaqueductal gray in modulating anxiety-like responses.

Yinan Du, Aozhuo Zhang, Zhiwei Li, Yukui Zhao, Shuyi Liu, Chunling Wei, Qiaohua Zheng, Yanning Qiao, Yihui Liu, Wei Ren and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Behavioral and brain functions : BBF, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Dorsal raphe nucleus enkephalin peptide modulates behavioral preference.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Yinan Du *Department of Neurology, The First Affiliated Hospital of Xi'an Medical University, Xi'an, 710061, Shaanxi, China. duyinansnnu@snnu.edu.cn.
Aozhuo Zhang *MOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi'an, 710062, China.
Zhiwei LiMOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi'an, 710062, China.
Yukui ZhaoMOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi'an, 710062, China.
Shuyi LiuMOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi'an, 710062, China.
Chunling WeiMOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi'an, 710062, China.
Qiaohua ZhengMOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi'an, 710062, China.
Yanning QiaoMOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi'an, 710062, China.
Yihui LiuMOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi'an, 710062, China.
Wei RenMOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi'an, 710062, China.
Jing HanMOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi'an, 710062, China.
Zhiqiang LiuMOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi'an, 710062, China.
Fei GaoDepartment of Neurology, The First Affiliated Hospital of Xi'an Medical University, Xi'an, 710061, Shaanxi, China.

Funding

National Natural Science Foundation of China 82071516National Natural Science Foundation of China 91949105the Science and Technology Innovation Team Project of Xi'an Medical University 2021TD14
6 · The paper itself

Abstract

backgroundMu-opioid receptors (MORs) are critical regulators mediating the modulation of several behavioral reactions, including analgesia, addiction, and sedation. Recent studies have reported that MORs are closely associated with mood disorders or anxiety behaviors; however, the underlying neural mechanisms remain unclear. The periaqueductal gray (PAG), a key brain area, participates in the modulation of aversive emotional behaviors. MORs show a high expression in the ventrolateral PAG (vlPAG) region. This study explored the preliminary role of MORs expressed in the vlPAG in modulating emotional behaviors.

resultsBilateral administration of DAMGO, an MOR-specific agonist, into the vlPAG of male mice elicited anxiety-like behaviors in elevated plus maze tests. This phenotype was reversed by conditional knockdown of astrocytic MORs. In contrast, glutamatergic or GABAergic MORs were not involved in vlPAG MOR-dependent anxiety-like behaviors. By using in vitro calcium imaging of vlPAG astrocytes and chemical genetic technologies, we found that vlPAG astrocytic MORs can promote astrocytic calcium signaling, which can efficiently induce anxiety-like behaviors. Accordingly, the interference of astrocytic calcium signaling by viral infection reversed vlPAG-dependent anxiety-like behaviors.

conclusionOur findings demonstrated that vlPAG astrocytic, but not glutamatergic or GABAergic, MORs are involved in modulating emotional reactions, and these effects are accomplished by MOR-elicited astrocytic calcium signaling mechanisms. The present study provides a theoretical basis for treating emotional dysfunctions during MOR-targeted management.

Indexed as

AnxietyAstrocytesPeriaqueductal GrayReceptors, Opioid, muAnalgesics, OpioidAnimalsCalcium SignalingEnkephalin, Ala(2)-MePhe(4)-Gly(5)-MaleMiceMice, Inbred C57BLAnalgesics, OpioidEnkephalin, Ala(2)-MePhe(4)-Gly(5)-Receptors, Opioid, muAnxietyAstrocyteCalcium signalingMu-opioid receptorsPeriaqueductal gray

Identifiers

PMID40702536
PMCPMC12285117

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.