Cholecystokinin B Receptor Antagonists For The Treatment Of Depression Via Blocking Longterm Potentiation In The Basolateral Amygdala Xu Zhang Muhammad Asim Wei Fang Hossain Md Monir Huajie Wang Kyuhee Kim Hemin Feng Shujie Wang Qianqian Gao Yuanying Lai Jufang He by Xu Zhang & Muhammad Asim & Wei Fang & Hossain Md Monir & Huajie Wang & Kyuhee Kim & Hemin Feng & Shujie Wang & Qianqian Gao & Yuanying Lai & Jufang He instant download after payment.

Depression is a common and severe mental disorder. Evidence suggested a substantial causal relationship between stressful lifeevents and the onset of episodes of major depression. However, the stress-induced pathogenesis of depression and the relatedneural 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 the1234567890();,:BLA, while the application of CCK4 induced LTP after low-frequency stimulation (LFS). The entorhinal cortex (EC) CCK neuronsproject 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 impairedLTP 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.