Lipids are predominant components of the brain and key regulators for neural structure and function. The neuropsychopharmacological effect of cocaine has been intensively investigated; however, the impact of cocaine on brain lipid profiles is largely unknown. In this study, we used a LC-MS-based lipidomic approach to investigate the impact of cocaine on brain lipidome in two mouse models, cocaine-conditioned place preference (CPP) and hyperlocomotor models and the lipidome was profoundly modified in the nucleus accumbens (NAc) and striatum respectively. We comprehensively analyzed the lipids among 21 subclasses across 7 lipid classes and found that cocaine profoundly modified brain lipidome. Notably, the lipid metabolites significantly modified were sphingolipids and glycerophospholipids in the NAc, showing a decrease in ceramide and an increase in its up/downstream metabolites levels, and decrease lysophosphatidylcholine (LPC) and lysophosphoethanolamine (LPE) and increase phosphatidylcholine (PC) and phosphatidylethanolamines (PE) levels, respectively. Moreover, long and polyunsaturated fatty acid phospholipids were also markedly increased in the NAc. Our results show that cocaine can markedly modify brain lipidomic profiling. These findings reveal a link between the modified lipidome and psychopharmacological effect of cocaine, providing a new insight into the mechanism of cocaine addiction.

脂质是大脑的主要成分，也是神经结构和功能的关键调节因子。可卡因的神经心理药理作用已得到深入研究。然而，可卡因对脑血脂的影响在很大程度上尚不清楚。在这项研究中，我们使用了基于LC-MS的脂质组学方法来研究可卡因对两种小鼠模型（可卡因条件位置偏爱（CPP）和运动亢进模型）的脑脂质组的影响，并且脂质组在伏隔核中进行了深刻修饰（ NAc）和纹状体。我们对7个脂质类别中的21个亚类中的脂质进行了全面分析，发现可卡因深刻修饰了脑脂质组。值得注意的是，NAc中的鞘脂和甘油磷脂被显着修饰的脂质代谢产物，分别显示神经酰胺减少和其上游/下游代谢产物水平增加，溶血磷脂酰胆碱（LPC）和溶血磷脂乙醇胺（LPE）降低，磷脂酰胆碱（PC）和磷脂酰乙醇胺（PE）水平升高。此外，长和多不饱和脂肪酸磷脂在NAc中也显着增加。我们的结果表明，可卡因可以显着改变脑脂质组学分析。这些发现揭示了修饰的脂质组和可卡因的心理药理作用之间的联系，为可卡因成瘾的机理提供了新的见识。长和多不饱和脂肪酸磷脂在NAc中也显着增加。我们的结果表明，可卡因可以显着改变脑脂质组学分析。这些发现揭示了修饰的脂质组和可卡因的心理药理作用之间的联系，为可卡因成瘾的机理提供了新的见识。长和多不饱和脂肪酸磷脂在NAc中也显着增加。我们的结果表明，可卡因可以显着改变脑脂质组学分析。这些发现揭示了修饰的脂质组和可卡因的心理药理作用之间的联系，为可卡因成瘾的机理提供了新的见识。