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

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

doi:10.1016/j.pbb.2023.173633

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

Pharmacol Biochem Behav. 2023 Oct:231:173633. doi: 10.1016/j.pbb.2023.173633. Epub 2023 Sep 15.

Affiliations

¹ Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA.
² Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
³ Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA; Translational Drug Development Core, Clinical and Translational Science Institute, University of Florida, Gainesville, FL, USA; Department of Medicinal Chemistry, University of Florida, Gainesville, FL, USA.
⁴ Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA; Translational Drug Development Core, Clinical and Translational Science Institute, University of Florida, Gainesville, FL, USA.
⁵ Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA. Electronic address: thanos@buffalo.edu.

PMID: 37716413
DOI: 10.1016/j.pbb.2023.173633

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.

Keywords: Endocannabinoid system; Fatty acid binding protein; Locomotion; Memory; Pharmacokinetics; Δ9-tetrahydrocannibinol.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / metabolism
Chromatography, Liquid
Cognition
Dronabinol* / pharmacology
Fatty Acid-Binding Proteins* / genetics
Fatty Acid-Binding Proteins* / metabolism
Fatty Acid-Binding Proteins* / pharmacology
Mice
Tandem Mass Spectrometry*

Substances

Dronabinol
Fatty Acid-Binding Proteins
Fabp5 protein, mouse