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Amygdala FAAH and anandamide: mediating protection and recovery from stress.
Trends Pharmacol Sci. 2013 Nov; 34(11):637-44.TP

Abstract

A long-standing literature linking endocannabinoids (ECBs) to stress, fear, and anxiety has led to growing interest in developing novel anxiolytics targeting the ECB system. Following rapid on-demand biosynthesis and degradation upon neuronal activation, the ECB N-arachidonoylethanolamide (anandamide, AEA) is actively degraded by the serine hydrolase enzyme, fatty acid amide hydrolase (FAAH). Exposure to stress rapidly mobilizes FAAH to deplete the signaling pool of AEA and increase neuronal excitability in a key anxiety-mediating region--the basolateral amygdala (BLA). Gene deletion or pharmacological inhibition of FAAH prevents stress-induced reductions in AEA and associated increases in BLA dendritic hypertrophy and anxiety-like behavior. Additionally, inhibition of FAAH facilitates long-term fear extinction and rescues deficient fear extinction in rodent models by enhancing AEA-CB1 (cannabinoid type 1) receptor signaling and synaptic plasticity in the BLA. These preclinical findings propose restoring deficient BLA AEA levels by pharmacologically inhibiting FAAH as a mechanism to therapeutically mitigate the effects of traumatic stress.

Authors+Show Affiliations

Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health, Bethesda, MD, USA. Electronic address: ozge.gunduzcinar@nih.gov.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

Language

eng

PubMed ID

24325918

Citation

Gunduz-Cinar, Ozge, et al. "Amygdala FAAH and Anandamide: Mediating Protection and Recovery From Stress." Trends in Pharmacological Sciences, vol. 34, no. 11, 2013, pp. 637-44.
Gunduz-Cinar O, Hill MN, McEwen BS, et al. Amygdala FAAH and anandamide: mediating protection and recovery from stress. Trends Pharmacol Sci. 2013;34(11):637-44.
Gunduz-Cinar, O., Hill, M. N., McEwen, B. S., & Holmes, A. (2013). Amygdala FAAH and anandamide: mediating protection and recovery from stress. Trends in Pharmacological Sciences, 34(11), 637-44. https://doi.org/10.1016/j.tips.2013.08.008
Gunduz-Cinar O, et al. Amygdala FAAH and Anandamide: Mediating Protection and Recovery From Stress. Trends Pharmacol Sci. 2013;34(11):637-44. PubMed PMID: 24325918.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amygdala FAAH and anandamide: mediating protection and recovery from stress. AU - Gunduz-Cinar,Ozge, AU - Hill,Matthew N, AU - McEwen,Bruce S, AU - Holmes,Andrew, Y1 - 2013/10/25/ PY - 2013/06/30/received PY - 2013/08/27/revised PY - 2013/08/29/accepted PY - 2013/12/12/entrez PY - 2013/12/12/pubmed PY - 2014/1/28/medline KW - 2-AG KW - anxiety KW - depression KW - endocannabinoid KW - fear KW - post-traumatic stress disorder SP - 637 EP - 44 JF - Trends in pharmacological sciences JO - Trends Pharmacol Sci VL - 34 IS - 11 N2 - A long-standing literature linking endocannabinoids (ECBs) to stress, fear, and anxiety has led to growing interest in developing novel anxiolytics targeting the ECB system. Following rapid on-demand biosynthesis and degradation upon neuronal activation, the ECB N-arachidonoylethanolamide (anandamide, AEA) is actively degraded by the serine hydrolase enzyme, fatty acid amide hydrolase (FAAH). Exposure to stress rapidly mobilizes FAAH to deplete the signaling pool of AEA and increase neuronal excitability in a key anxiety-mediating region--the basolateral amygdala (BLA). Gene deletion or pharmacological inhibition of FAAH prevents stress-induced reductions in AEA and associated increases in BLA dendritic hypertrophy and anxiety-like behavior. Additionally, inhibition of FAAH facilitates long-term fear extinction and rescues deficient fear extinction in rodent models by enhancing AEA-CB1 (cannabinoid type 1) receptor signaling and synaptic plasticity in the BLA. These preclinical findings propose restoring deficient BLA AEA levels by pharmacologically inhibiting FAAH as a mechanism to therapeutically mitigate the effects of traumatic stress. SN - 1873-3735 UR - https://www.unboundmedicine.com/medline/citation/24325918/Amygdala_FAAH_and_anandamide:_mediating_protection_and_recovery_from_stress_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0165-6147(13)00163-6 DB - PRIME DP - Unbound Medicine ER -