Evidence map›Paper›PMID 36221037›Full record

ArticlePsychopharmacology2022

Rapid antidepressant-like effects of muscarinic receptor antagonists require BDNF-dependent signaling in the ventrolateral periaqueductal gray.

Hung-Wei Kan, Wei-Hao Peng, Cheng-Chun Wu, Deng-Wu Wang, Ming Tatt Lee, Yung-Kuo Lee, Tian-Huei Chu, Yu-Cheng Ho

Abstract read
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In one paragraph

Article in Psychopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.2field-weighted citation impact, top 24% of its field
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

9 citing papers in PubMed, 13 citations in OpenAlex.

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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

8 authors at 4 institutions in 2 countries.

Hung-Wei KanSchool of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung City, 82445, Taiwan, Republic of China.
Wei-Hao PengSchool of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung City, 82445, Taiwan, Republic of China.
Cheng-Chun WuSchool of Medicine, College of Medicine, I-Shou University, No.8, Yida Rd., Yanchao District, Kaohsiung City, 82445, Taiwan, Republic of China.
Deng-Wu WangSchool of Medicine, College of Medicine, I-Shou University, No.8, Yida Rd., Yanchao District, Kaohsiung City, 82445, Taiwan, Republic of China.
Ming Tatt LeeFaculty of Pharmaceutical Sciences, UCSI University, 56000, Cheras, Kuala Lumpur, Malaysia.
Yung-Kuo LeeMedical Laboratory, Medical Education and Research Center, Kaohsiung Armed Forces General Hospital, Kaohsiung City, 80284, Taiwan, Republic of China.
Tian-Huei ChuMedical Laboratory, Medical Education and Research Center, Kaohsiung Armed Forces General Hospital, Kaohsiung City, 80284, Taiwan, Republic of China.
Yu-Cheng HoSchool of Medicine, College of Medicine, I-Shou University, No.8, Yida Rd., Yanchao District, Kaohsiung City, 82445, Taiwan, Republic of China. r96443003@ntu.edu.tw.
I-Shou University · TWKaohsiung Armed Forces General Hospital · TWNational Tsing Hua University · TWUCSI University · MY

Funding

Fundamental Research Grant Scheme, Ministry of Higher Education, Malaysia FRGS/1/2021/WAB13/UCSI/02/1Ministry of Science and Technology, Taiwan 108-2320-B-214-011-MY3Ministry of Science and Technology, Taiwan 109-2320-B-214-001Ministry of Science and Technology, Taiwan 110-2320-B-214-002Ministry of Science and Technology, Taiwan 110-2511-H-002-020-MY3Ministry of Science and Technology, Taiwan 111-2320-B-214 -002 -MY3Ministry of Science and Technology, Taiwan 111-2628-B-214 -001 -MY3UCSI University Research Excellence and Innovation Grant, Malaysia REIG-FPS-2020/065
6 · The paper itself

Abstract

rationaleClinical reports reveal that scopolamine, an acetylcholine muscarinic receptor antagonist, exerts rapid antidepressant effects in depressed patients, but the mechanisms underlying the therapeutic effects have not been fully identified.

objectivesThe present study examines the cellular mechanisms by which scopolamine produces antidepressant-like effects through its action in the ventrolateral midbrain periaqueductal gray (vlPAG).

methodsWe used a well-established mouse model of depression induced by chronic restraint stress (CRS) exposure for 14 days. Behaviors were tested using the forced swim test (FST), tail suspension test (TST), female urine sniffing test (FUST), novelty-suppressed feeding test (NSFT), and locomotor activity (LMA). Synaptic transmission in the vlPAG was measured by whole-cell patch-clamp recordings. IntravlPAG microinjection was used to pharmacologically verify the signaling cascades of scopolamine in the vlPAG.

resultsThe results demonstrated that intraperitoneal injection of scopolamine produced antidepressant-like effects in a dose-dependent manner without affecting locomotor activity. CRS elicited depression-like behaviors, whereas intraperitoneal injection of scopolamine alleviated CRS-induced depression-like behaviors. CRS diminished glutamatergic transmission in the vlPAG, while scopolamine reversed the above effects. Moreover, intravlPAG microinjection of the L-type voltage-dependent calcium channel (VDCC) blocker verapamil, tropomyosin-related kinase B (TrkB) receptor antagonist ANA-12, mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) antagonist CNQX prevented scopolamine-induced antidepressant-like effects.

conclusionsScopolamine ameliorated CRS-elicited depression-like behavior required activation of VDCC, resulting in activity-dependent release of brain-derived neurotrophic factor (BDNF), engaging the TrkB receptor and downstream mTORC1 signaling in the vlPAG.

Indexed as

Brain-Derived Neurotrophic FactorPeriaqueductal GrayAnimalsAntidepressive AgentsCalcium Channels, L-TypeDepressionFemaleMammalsMechanistic Target of Rapamycin Complex 1MiceMuscarinic AntagonistsReceptors, MuscarinicScopolamineAntidepressive AgentsBrain-Derived Neurotrophic FactorCalcium Channels, L-TypeMechanistic Target of Rapamycin Complex 1Muscarinic AntagonistsReceptors, MuscarinicScopolamineAMPA receptorBDNFDepressionElectrophysiologymTORC1Periaqueductal grayRestraint stressScopolamineSynaptic transmissionVoltage-dependent calcium channel

Identifiers

PMID36221037
OpenAlexW4304471388

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.