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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

Pharmacology, Biochemistry, and Behavior October 2023 DOI: 10.1016/j.pbb.2023.173633 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational animal study Peer reviewed
Population Adult FABP5+/+ and FABP5-/- mice
Intervention Δ9-tetrahydrocannabinol (THC)
Measures Open Field (OF), Novel Object Recognition (NOR), T-Maze, Morris Water Maze (MWM), Elevated Plus Maze (EPM), UPLC-MS/MS
Topics Cannabis
Keywords Endocannabinoid system Locomotion Memory Pharmacokinetics Δ9-tetrahydrocannibinol
Key findings The authors report that some cognitive deficits from FABP5 deletion, particularly in the Morris Water Maze, were blocked by THC administration, while other memory and anxiety measures (T-Maze and Elevated Plus Maze) were not. They also found that FABP5 alters the pharmacokinetics of THC, indicating it regulates THC's physiological effects.

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.

Comparable studies

Other preclinical and animal studies on cannabis, most cited first.

Study Year Design Participants
Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors Mice 2015 Preclinical study
Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). hMDR1- and hBCRP-transfected HEK293 cells and hMDR1- and hBCRP-MDCKII cells 2010 In vitro study
Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Mice prenatally exposed to THC, including conditional CB1R knockout mice 2020 Animal experimental study
Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway Mice exposed to chronic THC early in life 2018 Animal experimental study
Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain Spontaneously hypertensive rats (SHRs) and Wistar rats 2014 Animal experimental study

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