Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review
1
Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada
2
Centre for Addiction and Mental Health (CAMH), Toronto, ON M5T 1R8, Canada
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(3), 1047; https://doi.org/10.3390/ijms22031047
Received: 15 December 2020
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Revised: 15 January 2021
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Accepted: 18 January 2021
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Published: 21 January 2021
(This article belongs to the Special Issue Endocannabinoids, Cannabinoids and Psychiatry: Biological Mechanisms)
Altered activity of fatty acid amide hydrolase (FAAH), an enzyme of the endocannabinoid system, has been implicated in several neuropsychiatric disorders, including major depressive disorder (MDD). It is speculated that increased brain FAAH expression is correlated with increased depressive symptoms. The aim of this scoping review was to establish the role of FAAH expression in animal models of depression to determine the translational potential of targeting FAAH in clinical studies. A literature search employing multiple databases was performed; all original articles that assessed FAAH expression in animal models of depression were considered. Of the 216 articles that were screened for eligibility, 24 articles met inclusion criteria and were included in this review. Three key findings emerged: (1) FAAH expression is significantly increased in depressive-like phenotypes; (2) genetic knockout or pharmacological inhibition of FAAH effectively reduces depressive-like behavior, with a dose-dependent effect; and (3) differences in FAAH expression in depressive-like phenotypes were largely localized to animal prefrontal cortex, hippocampus and striatum. We conclude, based on the animal literature, that a positive relationship can be established between brain FAAH level and expression of depressive symptoms. In summary, we suggest that FAAH is a tractable target for developing novel pharmacotherapies for MDD.
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Keywords:
endocannabinoids; fatty acid amide hydrolase; major depressive disorder; animal models of depression
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MDPI and ACS Style
Rafiei, D.; Kolla, N.J. Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review. Int. J. Mol. Sci. 2021, 22, 1047. https://doi.org/10.3390/ijms22031047
AMA Style
Rafiei D, Kolla NJ. Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review. International Journal of Molecular Sciences. 2021; 22(3):1047. https://doi.org/10.3390/ijms22031047
Chicago/Turabian StyleRafiei, Dorsa, and Nathan J. Kolla. 2021. "Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review" International Journal of Molecular Sciences 22, no. 3: 1047. https://doi.org/10.3390/ijms22031047
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