The role of fatty acid-binding protein 5 and 7 on locomotor, anxiety and social behavior: Interaction with NMDA signaling.

The endocannabinoid system has been shown to be a powerful mediator of anxiety, learning and memory, as well as nociception behaviors. Exogenous cannabinoids like delta-9-tetrahydrocannabinol mimic the naturally occurring endogenous cannabinoids found in the mammalian central and peripheral nervous system. The hydrophobic properties of endocannabinoids mean that these psychoactive compounds require help with cellular transport. A family of lipid intracellular carriers called fatty acid-binding proteins (FABPs) can bind to endocannabinoids. Pharmacological inhibition or genetic deletion of FABP subtypes 5 and 7 elevates whole-brain anandamide (AEA) levels, a type of endocannabinoid. This study examined locomotor behavior, anxiety-like behavior, and social behavior in FABP5-/- and FABP7-/- mice. Furthermore, we measured N-methyl-D-aspartate (NMDA) receptor levels in the brain to help identify potential underlying mechanisms related to the behavioral findings. Results showed that both male and female FABP5-/- mice exhibited significantly lower activity when compared with both FABP5/7+/+ (control) and FABP7-/-. For social behavior, male, but not female, FABP5-/- mice spent more time interacting with novel mice compared with controls (FABP5/7+/+) and FABP7-/- mice. No significant difference was found for anxiety-like behavior. Results from the NMDA autoradiography revealed [3H] MK-801 binding to be significantly increased within sub-regions of the striatum in FABP7-/- compared with control. In summary, these results show that FABP5 deficiency plays a significant role in locomotion activity, exploratory behavior, as well as social interaction. Furthermore, FABP7 deficiency is shown to play an important role in NMDA receptor expression, while FABP5 does not.

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

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.

Effects of Δ9-Tetrahydrocannibinol (THC) on Obesity at Different Stages of Life: A Literature Review.

The Cannabis sativa plant has historically been used for both recreational and medical purposes. With the recent surge in recreational use of cannabis among adolescents and adults in particular, there is an increased obligation to determine the short- and long-term effects that consuming this plant may have on several aspects of the human psyche and body. The goal of this article was to examine the negative effects of obesity, and how the use of Δ9-tetrahydrocannibinol (THC) or cannabidiol (CBD) can impact rates of this global pandemic at different timepoints of life. Conflicting studies have been reported between adult and adolescents, as there are reports of THC use leading to increased weight due to elevated appetite and consumption of food, while others observed a decrease in overall body weight due to the regulation of omega-6/omega-3 endocannabinoid precursors and a decrease in energy expenditure. Studies supported a positive correlation between prenatal cannabis use and obesity rates in the children as they matured. The data did not indicate a direct connection between prenatal THC levels in cannabis and obesity rates, but that this development may occur due to prenatal THC consumption leading to low birthweight, and subsequent obesity. There are few studies using animal models that directly measure the effects that prenatal THC administration on obesity risks among offspring. Thus, this is a critical area for future studies using a developmental framework to examine potential changes in risk across development.