研究发现，可卡因能上调海马区突触传递长时程增强（LTP）并增加AMPA受体膜表达。caspase-1选择性抑制AMPA受体介导的电流，负性调控LTP。我们预实验发现，caspase-1基因敲除小鼠海马区LTP增强，另外观察到腹腔注射可卡因7天后小鼠海马区caspase-1 p20亚基表达显著降低。据此设想，慢性可卡因应激诱导海马区caspase-1活性降低，减少对AMPA受体的剪切，使AMPA受体功能增强，易化LTP，参与成瘾记忆的发生发展。基于此，本项目拟通过建立慢性可卡因暴露的体外及动物模型，调控caspase-1信号通路，观察突触可塑性及成瘾行为改变。探讨caspase-1活性调节AMPA受体膜表达的机制及其在可卡因成瘾中的作用，有助于深入理解caspase-1剪切膜表达受体的病理生理意义，为可卡因及其他精神活性物质成瘾的防治提供新思路和新靶点。

Previous studies demonstrate that cocaine increases hippocampal (long-term potentiation) LTP and the surface expression of AMPA receptor. It has been reported that caspase-1 inhibits AMPA receptor-mediated current selectively and regulates hippocampal long-term potentiation (LTP) negatively. Our preliminary experiment showed the facilitation of LTP in caspase-1 knockout mice, and also found that the chronic cocaine exposure decreased the expression of caspase-1 p20 subunit. Therefore, we hypothesized that chronic cocaine exposure induced the decrease in caspase-1 activity, and inhibited the cleavage of AMPA receptor by caspase-1, thus facilitated LTP, which contributed to cocaine addiction. In this study, the in vitro and in vivo chronic cocaine exposure was employed. The effects of regulation of caspase-1 signaling pathway on synaptic plasticity and behavior changes were observed. The study on regulation of surface expression of AMPA receptor by caspase-1 in cocaine addiction is helpful to understand the pathophysiological role of receptor cleaved by caspase-1, and provide new target and strategy for the treatment of cocaine and other psychoactive drugs.