| First Author | Zhang X | Year | 2023 |
| Journal | Mol Psychiatry | Volume | 28 |
| Issue | 8 | Pages | 3459-3474 |
| PubMed ID | 37365241 | Mgi Jnum | J:359181 |
| Mgi Id | MGI:7785404 | Doi | 10.1038/s41380-023-02127-7 |
| Citation | Zhang X, et al. (2023) Cholecystokinin B receptor antagonists for the treatment of depression via blocking long-term potentiation in the basolateral amygdala. Mol Psychiatry 28(8):3459-3474 |
| abstractText | Depression is a common and severe mental disorder. Evidence suggested a substantial causal relationship between stressful life events and the onset of episodes of major depression. However, the stress-induced pathogenesis of depression and the related neural circuitry is poorly understood. Here, we investigated how cholecystokinin (CCK) and CCKBR in the basolateral amygdala (BLA) are implicated in stress-mediated depressive-like behavior. The BLA mediates emotional memories, and long-term potentiation (LTP) is widely considered a trace of memory. We identified that the cholecystokinin knockout (CCK-KO) mice impaired LTP in the BLA, while the application of CCK4 induced LTP after low-frequency stimulation (LFS). The entorhinal cortex (EC) CCK neurons project to the BLA and optogenetic activation of EC CCK afferents to BLA-promoted stress susceptibility through the release of CCK. We demonstrated that EC CCK neurons innervate CCKBR cells in the BLA and CCK-B receptor knockout (CCKBR-KO) mice impaired LTP in the BLA. Moreover, the CCKBR antagonists also blocked high-frequency stimulation (HFS) induced LTP formation in the BLA. Notably, CCKBR antagonists infusion into the BLA displayed an antidepressant-like effect in the chronic social defeat stress model. Together, these results indicate that CCKBR could be a potential target to treat depression. |
