| First Author | Zhang Y | Year | 2024 |
| Journal | Acta Pharm Sin B | Volume | 14 |
| Issue | 2 | Pages | 667-681 |
| PubMed ID | 38322327 | Mgi Jnum | J:349333 |
| Mgi Id | MGI:7647037 | Doi | 10.1016/j.apsb.2023.12.005 |
| Citation | Zhang Y, et al. (2024) Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy. Acta Pharm Sin B 14(2):667-681 |
| abstractText | 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. |
