DataVXAdvanced SciencePaper
journal article·2025-04Open access

Prefrontal FGF1 Signaling is Required for Accumbal Deep Brain Stimulation Treatment of Addiction

Wan‐Kun Gong, Xue Li, Le Wang, Qian Yang, Alix Tiran‐Cappello, Zhichao Liang, James Samsom, Quanying Liu, He Lin, Christelle Baunez, Fang Liu, Ti‐Fei Yuan

Advanced Science· Volume 12· Issue 16
Publisher pageOpen full text
Source abstract

Abstract

Abstract Deep brain stimulation (DBS) has emerged as a prospective treatment for psychiatric disorders; for example, DBS targeting the nucleus accumbens (NAc) abolishes addictive behaviors. However, neither the core pathway nor the cellular mechanisms underlying these therapeutic effects are known. Here, morphine‐induced conditioned place preference (CPP) in mice as an addiction model and NAc‐DBS combined with adeno‐associated virus gene delivery for activity‐dependent tagging, transgenic and chemogenetic manipulation of recruited neuronal networks are used. It is reported that a cortical‐accumbal pathway and local fibroblast growth factor 1 (FGF1) signaling in the medial prefrontal cortex (mPFC) are critical for NAc‐DBS to be effective in altering morphine CPP. It is shown that NAc‐DBS retrogradely activates mPFC neurons projecting to the NAc, and chemogenetic activation/inhibition of these DBS‐activated neuron ensembles in the mPFC reproduces the NAc‐DBS effects on CPP. Sustained therapeutic effects accompany reductions in local FGF1 binding to fibroblast growth factor receptor 1 (FGFR1) in these neurons. Additionally, overexpressing FGF1 in the mPFC‐NAc pathway abolishes the therapeutic effects of NAc‐DBS. These results demonstrate that the mPFC‐NAc pathway forms a top‐down motif to regulate the therapeutic effects of subcortical DBS on addiction. These results support the potential for addiction treatments involving FGF1 signaling and highlight the mPFC as a target for noninvasive brain stimulation.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Neurological disorders and treatments · Transcranial Magnetic Stimulation Studies · Obsessive-Compulsive Spectrum Disorders

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Shanghai Key Laboratory of Psychotic Disorders Brain Health Institute National Center for Mental Disorders Shanghai Mental Health Center Shanghai Jiaotong University School of Medicine and School of Psychology Shanghai 200030 China

Co‐innovation Center of Neuroregeneration Nantong University Nantong Jiangsu 226019 China

Department of Clinical Laboratory Diagnosis Changhai Hospital Shanghai 200433 China

Institute of Mental Health and Drug Discovery, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine Vision and Brain Health), School of Mental Health Wenzhou Medical University Wenzhou Zhejiang 325000 China

Institut de Neurosciences de la Timone UMR7289 CNRS & Aix‐Marseille Université Marseille France

Shenzhen Key Laboratory of Smart Healthcare Engineering Department of Biomedical Engineering Southern University of Science and Technology Shenzhen 518055 China

Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health Toronto ON M5T1R8 Canada

The Third Research Institute of Ministry of Public Security Shanghai 200438 China

Department of Psychiatry, Physiology, Pharmacology and Toxicology and Institutes of Medical Science University of Toronto Toronto ON M5T 1R8 Canada

Funding

National Outstanding Youth Science Fund Project of National Natural Science Foundation of China · International Science and Technology Cooperation Programme · Major Research Plan · National Natural Science Foundation of China · Science and Technology Commission of Shanghai Municipality · Shanghai Municipal Education Commission · China Postdoctoral Science Foundation

References (34)

Show source-provided references
1. 10.1016/0140-6736(91)91175-T10.1016/0140-6736(91)91175-T ↗
2. 10.1016/S0140-6736(95)90062-410.1016/S0140-6736(95)90062-4 ↗
3. 10.1073/pnas.202412111810.1073/pnas.2024121118 ↗
4. 10.1038/s41380-018-0080-y10.1038/s41380-018-0080-y ↗
5. 10.1073/pnas.090818910710.1073/pnas.0908189107 ↗
6. 10.3389/fpsyt.2023.114649210.3389/fpsyt.2023.1146492 ↗
7. 10.1016/j.wneu.2018.11.05610.1016/j.wneu.2018.11.056 ↗
8. 10.1016/j.biopsych.2015.06.02310.1016/j.biopsych.2015.06.023 ↗
9. 10.1126/science.126077610.1126/science.1260776 ↗
10. 10.1016/j.biopsych.2016.05.01510.1016/j.biopsych.2016.05.015 ↗
11. 10.1038/tp.2016.10010.1038/tp.2016.100 ↗
12. 10.1038/nature1325710.1038/nature13257 ↗
13. 10.1038/nature1070910.1038/nature10709 ↗
14. 10.1038/nrn311910.1038/nrn3119 ↗
15. 10.1073/pnas.93.21.1204010.1073/pnas.93.21.12040 ↗
16. 10.1038/mp.2011.18410.1038/mp.2011.184 ↗
17. 10.1523/JNEUROSCI.2317-15.201510.1523/JNEUROSCI.2317-15.2015 ↗
18. 10.1016/j.neurom.2022.04.03510.1016/j.neurom.2022.04.035 ↗
19. 10.1016/B978-0-444-53815-4.00013-310.1016/B978-0-444-53815-4.00013-3 ↗
20. 10.1038/jcbfm.2011.4110.1038/jcbfm.2011.41 ↗
21. 10.1073/pnas.151924811310.1073/pnas.1519248113 ↗
22. 10.1016/j.neuroscience.2009.10.00910.1016/j.neuroscience.2009.10.009 ↗
23. 10.1016/j.bbr.2014.12.02510.1016/j.bbr.2014.12.025 ↗
24. 10.1038/s41398-023-02727-510.1038/s41398-023-02727-5 ↗
25. 10.1523/JNEUROSCI.5277-07.200810.1523/JNEUROSCI.5277-07.2008 ↗
26. 10.1046/j.1460-9568.2003.02803.x10.1046/j.1460-9568.2003.02803.x ↗
27. 10.1126/sciadv.add664210.1126/sciadv.add6642 ↗
28. 10.1016/j.neuron.2020.06.02810.1016/j.neuron.2020.06.028 ↗
29. Lueptow L. M. · J. Vis. Exp. · 2017
30. 10.1088/1741-2552/ab6e8b10.1088/1741-2552/ab6e8b ↗
31. 10.1016/j.neuron.2023.02.01710.1016/j.neuron.2023.02.017 ↗
32. 10.1038/nmeth.255910.1038/nmeth.2559 ↗
33. 10.1016/j.neuron.2022.07.00410.1016/j.neuron.2022.07.004 ↗
34. 10.1038/s41422-021-00588-510.1038/s41422-021-00588-5 ↗