Fatty acid binding protein 5 (FABP5) interacts with the endocannabinoid system in the brain via intracellular transport of anandamide, as well as Δ9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis. Previous work has established the behavioral effects of genetic deletion of FABP5, but not in the presence of THC. The present study sought to further elucidate the role of FABP5 on the pharmacokinetic and behavioral response to THC through global deletion. Adult FABP5^+/+ and FABP5^−/− mice were tested for behavioral response to THC using Open Field (OF), Novel Object Recognition (NOR), T-Maze, Morris Water Maze (MWM), and Elevated Plus Maze (EPM). An additional cohort of mice was used to harvest blood, brains, and liver samples to measure THC and metabolites after acute administration of THC. Behavioral tests showed that some cognitive deficits from FABP5 deletion, particularly in MWM, were blocked by THC administration, while this was not observed in other measures of memory and anxiety (such as T-Maze and EPM). Measurement of THC and metabolites in blood serum and brain tissue through UPLC-MS/MS analysis showed that the pharmacokinetics of THC was altered by FABP5. The present study shows further evidence of the importance of FABP5 in cognitive function. Additionally, results showed that FABP5 is an important regulator of the physiological effects and pharmacokinetics of THC.

脂肪酸结合蛋白5 (FABP5) 通过细胞内转运anandamide 以及大麻的主要精神活性成分 Δ9-四氢大麻酚 (THC)与大脑中的内源性大麻素系统相互作用。之前的工作已经确定了 FABP5基因缺失对行为的影响，但在 THC 存在的情况下则不然。本研究试图通过整体删除进一步阐明 FABP5 对 THC 的药代动力学和行为反应的作用。使用开放场 (OF)、新物体识别 (NOR)、T 迷宫、莫里斯水迷宫(MWM) 和高架十字迷宫 (EPM)测试成年 FABP5 ^+/+和 FABP5^-/−小鼠对 THC 的行为反应。另一组小鼠被用来采集血液、大脑和肝脏样本，以测量急性施用 THC 后的 THC 和代谢物。行为测试表明， FABP5 缺失导致的一些认知缺陷，特别是在 MWM 中，可以被 THC 给药阻断，而在其他记忆和焦虑测量（例如 T-Maze 和 EPM）中没有观察到这种情况。通过 UPLC-MS/MS 分析测量血清和脑组织中的 THC 和代谢物表明 FABP5 改变了 THC 的药代动力学。本研究进一步证明 FABP5 在认知功能中的重要性。此外，结果表明 FABP5 是 THC 生理效应和药代动力学的重要调节因子。