Adapter protein 2-modulated μ-opioid receptor trafficking in paraventricular thalamus contributes to fentanyl contextual addiction memory in mice
文献类型：期刊论文
| 作者 | Li, Yu-jie2; Chen, Ruo-song3; Zan, Gui-ying4,5; Song, Ying-cai6; Huang, Xue-ying7; Zhang, Bing6; Du, Wei-jia6; Yuan, Ti-fei1,8,9; Liu, Zhi-qiang6 |
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2025-12-01 |
| 页码 | 9 |
| 关键词 | fentanyl contextual addiction memory paraventricular thalamus mu-opioid receptor trafficking Ap2a1 |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/s41401-025-01684-7 |
| 英文摘要 | Fentanyl and its analogues are the most commonly used synthetic opioid analgesics in clinical practice, but their abuse is a significant concern. Drug-paired environmental cues often trigger memory retrieval, leading to relapse, complicating treatment and overdose prevention. In this study we investigated mu-opioid receptor-related molecular mechanisms underlying the retrieval of fentanyl contextual addiction memory in mice. A conditional place preference (CPP) model was established in mice by citrate injections of fentanyl (0.1 mg/kg) for 4 days. By performing whole-brain screening using c-Fos immunofluorescence staining, we found that the paraventricular thalamus (PVT) was dramatically activated. We conducted Western blotting, co-immunoprecipitation and proteomics to evaluate the proteins interacting with mu-opioid receptors on the membrane, and found marked externalization of mu-opioid receptors on the membrane in PVT neurons. We revealed that mu-opioid receptors trafficking in PVT was regulated by the extent of binding of Ap2a1 to the membrane mu-opioid receptors. By conditional knockdown and chemogenetic manipulation, we demonstrated the contribution of mu-opioid receptors to the retrieval of fentanyl contextual memory via modulating the neuronal activity in PVT. In conclusion, this study suggests that Ap2a1-mediated trafficking of mu-opioid receptors underlies the retrieval of fentanyl contextual addiction memory through regulating the neuronal activity in PVT. |
| WOS关键词 | MORPHINE-TOLERANCE ; DESENSITIZATION ; ACTIVATION ; PHOSPHORYLATION ; INTERNALIZATION ; DYNORPHIN ; NUCLEUS |
| 资助项目 | National Natural Science Foundation of China[82371533] ; National Natural Science Foundation of China[82301677] ; Natural Science Foundation of Shanghai[22ZR1449300] ; Program of Shanghai Academic/Technology Research Leader[22XD1402400] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001627956300001 |
| 出版者 | NATURE PUBL GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322073]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Du, Wei-jia; Yuan, Ti-fei; Liu, Zhi-qiang |
| 作者单位 | 1.Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong 226019, Peoples R China 2.Tongji Univ, Shanghai Matern & Infant Hosp 1, Shanghai Inst Maternal Fetal Med & Gynecol Oncol, Sch Med,Dept Anesthesiol,Shanghai Key Lab Maternal, Shanghai 200092, Peoples R China 3.Zhejiang Chinese Med Univ, Clin Med Coll 3, Dept Neurobiol & Acupuncture Res, Key Lab Acupuncture & Neurobiol Zhejiang Prov, Hangzhou 310053, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 6.Fudan Univ, Obstetr & Gynecol Hosp, Shanghai Key Lab Reprod & Dev,Dept Anesthesiol, Shanghai Key Lab Female Reprod Endocrine Related D, Shanghai 200433, Peoples R China 7.Tongji Univ, Shanghai Matern & Infant Hosp 1, Shanghai Inst Maternal Fetal Med & Gynecol Oncol, Shanghai Key Lab Maternal Fetal Med,Sch Med, Shanghai 200092, Peoples R China 8.Shanghai Jiao Tong Univ, Shanghai Key Lab Psychot Disorders, Brain Hlth Inst,Sch Med, Natl Ctr Mental Disorders,Shanghai Mental Hlth Ct, Shanghai 200030, Peoples R China 9.Shanghai Jiao Tong Univ, Sch Psychl, Shanghai 200030, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Yu-jie,Chen, Ruo-song,Zan, Gui-ying,et al. Adapter protein 2-modulated μ-opioid receptor trafficking in paraventricular thalamus contributes to fentanyl contextual addiction memory in mice[J]. ACTA PHARMACOLOGICA SINICA,2025:9. |
| APA | Li, Yu-jie.,Chen, Ruo-song.,Zan, Gui-ying.,Song, Ying-cai.,Huang, Xue-ying.,...&Liu, Zhi-qiang.(2025).Adapter protein 2-modulated μ-opioid receptor trafficking in paraventricular thalamus contributes to fentanyl contextual addiction memory in mice.ACTA PHARMACOLOGICA SINICA,9. |
| MLA | Li, Yu-jie,et al."Adapter protein 2-modulated μ-opioid receptor trafficking in paraventricular thalamus contributes to fentanyl contextual addiction memory in mice".ACTA PHARMACOLOGICA SINICA (2025):9. |
入库方式： OAI收割
来源：上海药物研究所
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