Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy
© 2024 The Authors..
Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Acta pharmaceutica Sinica. B - 14(2024), 2 vom: 01. Feb., Seite 667-681 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Yue [VerfasserIn] |
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| Links: |
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| Themen: |
CAMP |
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| Anmerkungen: |
Date Revised 10.02.2024 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.apsb.2023.12.005 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368115267 |
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| 520 | |a © 2024 The Authors. | ||
| 520 | |a Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Crocin | |
| 650 | 4 | |a D1-MSN | |
| 650 | 4 | |a D2-MSN | |
| 650 | 4 | |a Depression | |
| 650 | 4 | |a Ketamine | |
| 650 | 4 | |a Nucleus accumbens | |
| 650 | 4 | |a Rapid antidepressant | |
| 650 | 4 | |a cAMP | |
| 700 | 1 | |a Gao, Jingwen |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Na |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Qu, Shimeng |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Jinqian |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Mingrui |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xueru |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Yaheng |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Xinyu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jihong |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Mu, Ronghao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiaotian |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Youmei |e verfasserin |4 aut | |
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| 700 | 1 | |a Gao, Tianming |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Guangji |e verfasserin |4 aut | |
| 700 | 1 | |a Aa, Jiye |e verfasserin |4 aut | |
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