FABP5 is important for cognitive function and is an important regulator of the physiological effects and pharmacokinetics of acute Δ9 tetrahydrocannabinol inhalation in mice

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES Pharmacology Biochemistry and Behavior Pub Date : 2023-10-01 DOI:10.1016/j.pbb.2023.173633

Samantha L. Penman , Nicole M. Roeder , Erin C. Berthold , Alexandria S. Senetra , Matthew Marion , Brittany J. Richardson , Olivia White , Nathan L. Fearby , Christopher R. McCurdy , John Hamilton , Abhisheak Sharma , Panayotis K. Thanos

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Abstract

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.

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FABP5对认知功能很重要，是小鼠急性吸入Δ9四氢大麻酚的生理作用和药代动力学的重要调节因子。

脂肪酸结合蛋白5（FABP5）通过anandamide以及大麻的主要精神活性成分Δ9-四氢大麻酚（THC）的细胞内转运与大脑中的内源性大麻素系统相互作用。先前的工作已经确定了FABP5基因缺失的行为效应，但在THC存在的情况下没有。本研究试图通过整体缺失进一步阐明FABP5在四氢大麻酚的药代动力学和行为反应中的作用。使用开放场（OF）、新型物体识别（NOR）、T-Maze、Morris水迷宫（MWM）和Elevated Plus Maze（EPM）测试成年FABP5+/+和FABP5-/-小鼠对THC的行为反应。另一组小鼠被用于采集血液、大脑和肝脏样本，以测量急性给药后的四氢大麻酚和代谢产物。行为测试表明，FABP5缺失引起的一些认知缺陷，特别是在MWM中，被THC阻断，而在其他记忆和焦虑指标（如T-Maze和EPM）中没有观察到这一点。通过UPLC-MS/MS分析测定血清和脑组织中的四氢大麻酚及其代谢产物表明，FABP5改变了四氢大麻黄酮的药代动力学。本研究进一步证明了FABP5在认知功能中的重要性。此外，研究结果表明，FABP5是THC生理作用和药代动力学的重要调节因子。

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来源期刊

Pharmacology Biochemistry and Behavior 医学-行为科学

CiteScore

6.40

自引率

2.80%

发文量

122

审稿时长

38 days

期刊介绍： Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.