This review analyzes the roles of lipid transmitters, especially those derived from the cleavage of membrane phospholipids, in cocaine-associated behaviors. These lipid signals are important modulators of information processing in the brain, affecting transmitter release, neural plasticity, synaptogenesis, neurogenesis, and cellular energetics. This broad range of actions makes them suitable targets for pharmaceutical development of cocaine addiction therapies because they participate in the main cellular processes underlying the neuroadaptations associated with chronic use of this psychostimulant. The main lipid transmitters reviewed here include a) acylethanolamides and acylglycerols acting on cannabinoid receptors, such as anandamide and 2-arachidonoylglycerol; b) acylethanolamides that do not act on cannabinoid receptors, such as oleoylethanolamide; c) eicosanoids derived from arachidonic acid, including prostaglandins; and d) lysophosphatidic acid, focusing on the role of its LPA-1 receptor. Direct experimental evidence for the significance of these lipids in cocaine-related behaviors is presented and discussed. Additionally, the roles for both their biosynthesis and degradation pathways, as well as the participation of their receptors, are examined. Overall, lipid transmitter signaling can offer new targets for the development of therapies for cocaine addiction.

译文

这篇综述分析了脂质递质,尤其是源自膜磷脂裂解的脂质递质在可卡因相关行为中的作用。这些脂质信号是大脑中信息处理的重要调节剂,影响递质释放,神经可塑性,突触发生,神经发生和细胞能量学。这种广泛的作用使它们成为可卡因成瘾疗法药物开发的合适目标,因为它们参与了与长期使用这种精神兴奋剂相关的神经适应的主要细胞过程。此处审查的主要脂质递质包括a) 作用于大麻素受体的酰基乙醇胺和酰基甘油,例如anandamide和2-花生四烯基甘油; b) 不作用于大麻素受体的酰基乙醇胺,例如油酰乙醇酰胺; c) 源自花生四烯酸的类花生酸,包括前列腺素; 和d) 溶血磷脂酸,重点研究其LPA-1受体的作用。提出并讨论了这些脂质在可卡因相关行为中的重要性的直接实验证据。此外,还检查了它们的生物合成和降解途径的作用以及它们受体的参与。总体而言,脂质递质信号可以为开发可卡因成瘾疗法提供新的靶标。

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