Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review

Rafiei, Dorsa; Kolla, Nathan J.

doi:10.3390/ijms22031047

Cited by 14 publications

(9 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here, we focused on the relationship between FAAH binding and neuroticism in personality disorders. Our findings comport well with the animal literature linking pharmacological inhibition or genetic deletion of FAAH to the rescue of depressive and anxious phenotypes 36 . According to this model, decreased FAAH activity increases brain AEA levels and stimulates anxiolytic-like responses in a CB1R-dependent manner 37 .…”

Section: Discussionsupporting

confidence: 88%

Higher trait neuroticism is associated with greater fatty acid amide hydrolase binding in borderline and antisocial personality disorders

Kolla

Boileau

Bagby

2022

Sci Rep

Self Cite

View full text Add to dashboard Cite

Borderline personality disorder (BPD) and antisocial personality disorder (ASPD) are the two most frequently diagnosed and researched DSM-5 personality disorders, and both are characterized by high levels of trait neuroticism. Fatty acid amide hydrolase (FAAH), an enzyme of the endocannabinoid system (ECS), has been linked to regulation of mood through modulation of anandamide, an endocannabinoid. We hypothesized that prefrontal cortex (PFC) FAAH binding would relate to trait neuroticism in personality disorders. Thirty-one individuals with personality disorders (20 with BPD and 11 with ASPD) completed the investigation. All participants completed the revised NEO Personality Inventory, which yields standardized scores (e.g., T scores) for the traits of neuroticism, openness, conscientiousness, agreeableness, and extraversion. All participants were medication free and were not utilizing illicit substances as determined by drug urinalysis. Additionally, none of the participants had a comorbid major depressive episode, bipolar disorder, psychotic disorder, or substance use disorder. Each participant underwent one [11C]CURB PET scan. Consistent with our hypothesis, neuroticism was positively correlated with PFC FAAH binding (r = 0.42, p = 0.021), controlling for genotype. Neuroticism was also positively correlated with dorsal putamen FAAH binding (r = 0.53, p = 0.0024), controlling for genotype. Elevated brain FAAH is an endophenotype for high neuroticism in BPD and ASPD. Novel pharmacological therapeutics that inhibit FAAH could emerge as potential new treatments for BPD and ASPD with high neuroticism.

show abstract

Section: Discussionsupporting

confidence: 88%

Higher trait neuroticism is associated with greater fatty acid amide hydrolase binding in borderline and antisocial personality disorders

Kolla

Boileau

Bagby

2022

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Since scoparone did not modulate the FST behavior itself, we assume that this lipid remodeling was not causally involved in the FST behavior. Given the association of anandamide with depression-like behaviors in mice, this finding is unexpected because FAAH inhibitors are effective in the FST paradigm 34 .…”

Section: Discussionmentioning

confidence: 99%

Neuropsychopharmacological profiling of scoparone in mice

Kowalczyk

Budzyńska

Kurach

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Scoparone (6,7-dimethoxycoumarin) is a simple coumarin from botanical drugs of Artemisia species used in Traditional Chinese Medicine and Génépi liquor. However, its bioavailability to the brain and potential central effects remain unexplored. We profiled the neuropharmacological effects of scoparone upon acute and subchronic intraperitoneal administration (2.5–25 mg/kg) in Swiss mice and determined its brain concentrations and its effects on the endocannabinoid system (ECS) and related lipids using LC–ESI–MS/MS. Scoparone showed no effect in the forced swimming test (FST) but, administered acutely, led to a bell-shaped anxiogenic-like behavior in the elevated plus-maze test and bell-shaped procognitive effects in the passive avoidance test when given subchronically and acutely. Scoparone rapidly but moderately accumulated in the brain (Cmax < 15 min) with an apparent first-order elimination (95% eliminated at 1 h). Acute scoparone administration (5 mg/kg) significantly increased brain arachidonic acid, prostaglandins, and N-acylethanolamines (NAEs) in the FST. Conversely, subchronic scoparone treatment (2.5 mg/kg) decreased NAEs and increased 2-arachidonoylglycerol. Scoparone differentially impacted ECS lipid remodeling in the brain independent of serine hydrolase modulation. Overall, the unexpectedly potent central effects of scoparone observed in mice could have toxicopharmacological implications for humans.

show abstract

“…A recent comprehensive review by Rafiei and Kolla [254] proposed that FAAH expression is significantly increased in depressive-like phenotypes, and differences in FAAH expression in depressive phenotypes were primarily localized in the PFC, HIPP, and striatum of the animals. They conclude that FAAH may result in an appropriate target for developing new drugs for MDD.…”

Section: Animal Studiesmentioning

confidence: 99%

Molecular Alterations of the Endocannabinoid System in Psychiatric Disorders

Navarro

Gasparyan

Navarrete

et al. 2022

IJMS

View full text Add to dashboard Cite

The therapeutic benefits of the current medications for patients with psychiatric disorders contrast with a great variety of adverse effects. The endocannabinoid system (ECS) components have gained high interest as potential new targets for treating psychiatry diseases because of their neuromodulator role, which is essential to understanding the regulation of many brain functions. This article reviewed the molecular alterations in ECS occurring in different psychiatric conditions. The methods used to identify alterations in the ECS were also described. We used a translational approach. The animal models reproducing some behavioral and/or neurochemical aspects of psychiatric disorders and the molecular alterations in clinical studies in post-mortem brain tissue or peripheral tissues were analyzed. This article reviewed the most relevant ECS changes in prevalent psychiatric diseases such as mood disorders, schizophrenia, autism, attentional deficit, eating disorders (ED), and addiction. The review concludes that clinical research studies are urgently needed for two different purposes: (1) To identify alterations of the ECS components potentially useful as new biomarkers relating to a specific disease or condition, and (2) to design new therapeutic targets based on the specific alterations found to improve the pharmacological treatment in psychiatry.

show abstract

Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review

Cited by 14 publications

References 112 publications

Higher trait neuroticism is associated with greater fatty acid amide hydrolase binding in borderline and antisocial personality disorders

Higher trait neuroticism is associated with greater fatty acid amide hydrolase binding in borderline and antisocial personality disorders

Neuropsychopharmacological profiling of scoparone in mice

Molecular Alterations of the Endocannabinoid System in Psychiatric Disorders

Contact Info

Product

Resources

About