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Reduced anxiety-like behaviour induced by genetic and pharmacological inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) is mediated by CB1 receptors.
Neuropharmacology. 2008 Jan; 54(1):141-50.N

Abstract

Anandamide and 2-arachidonoyl glycerol, referred to as endocannabinoids (eCBs), are the endogenous agonists for the cannabinoid receptor type 1 (CB1). Several pieces of evidence support a role for eCBs in the attenuation of anxiety-related behaviours, although the precise mechanism has remained uncertain. The fatty acid amid hydrolase (FAAH), an enzyme responsible for the degradation of eCBs, has emerged as a promising target for anxiety-related disorders, since FAAH inhibitors are able to increase the levels of anandamide and thereby induce anxiolytic-like effects in rodents. The present study adopted both genetic and pharmacological approaches and tested the hypothesis that FAAH-deficient (FAAH(-/-)) mice as well as C57BL/6N mice treated with an FAAH inhibitor (URB597) would express reduced anxiety-like responses. Furthermore, as it is known that anandamide can bind several other targets than CB1 receptors, we investigated whether FAAH inhibition reduces anxiety via CB1 receptors. FAAH(-/-) mice showed reduced anxiety both in the elevated plus maze and in the light-dark test. These genotype-related differences were prevented by the CB1 receptor antagonist rimonabant (3mg/kg). Moreover, URB597 (1mg/kg) induced an anxiolytic-like effect in C57BL/6N mice exposed to the elevated plus maze, which was prevented by rimonabant (3mg/kg). The present work provides genetic and pharmacological evidence supporting the inhibition of FAAH as an important mechanism for the alleviation of anxiety. In addition, it indicates an increased activation of CB1 receptors as a mechanism underlying the effects of FAAH inhibition in two models of anxiety.

Authors+Show Affiliations

Department of Physiological Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 6, D-55099 Mainz, Germany.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17709120

Citation

Moreira, Fabricio A., et al. "Reduced Anxiety-like Behaviour Induced By Genetic and Pharmacological Inhibition of the Endocannabinoid-degrading Enzyme Fatty Acid Amide Hydrolase (FAAH) Is Mediated By CB1 Receptors." Neuropharmacology, vol. 54, no. 1, 2008, pp. 141-50.
Moreira FA, Kaiser N, Monory K, et al. Reduced anxiety-like behaviour induced by genetic and pharmacological inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) is mediated by CB1 receptors. Neuropharmacology. 2008;54(1):141-50.
Moreira, F. A., Kaiser, N., Monory, K., & Lutz, B. (2008). Reduced anxiety-like behaviour induced by genetic and pharmacological inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) is mediated by CB1 receptors. Neuropharmacology, 54(1), 141-50.
Moreira FA, et al. Reduced Anxiety-like Behaviour Induced By Genetic and Pharmacological Inhibition of the Endocannabinoid-degrading Enzyme Fatty Acid Amide Hydrolase (FAAH) Is Mediated By CB1 Receptors. Neuropharmacology. 2008;54(1):141-50. PubMed PMID: 17709120.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced anxiety-like behaviour induced by genetic and pharmacological inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) is mediated by CB1 receptors. AU - Moreira,Fabricio A, AU - Kaiser,Nadine, AU - Monory,Krisztina, AU - Lutz,Beat, Y1 - 2007/07/19/ PY - 2007/04/10/received PY - 2007/07/01/revised PY - 2007/07/04/accepted PY - 2007/8/22/pubmed PY - 2008/4/19/medline PY - 2007/8/22/entrez SP - 141 EP - 50 JF - Neuropharmacology JO - Neuropharmacology VL - 54 IS - 1 N2 - Anandamide and 2-arachidonoyl glycerol, referred to as endocannabinoids (eCBs), are the endogenous agonists for the cannabinoid receptor type 1 (CB1). Several pieces of evidence support a role for eCBs in the attenuation of anxiety-related behaviours, although the precise mechanism has remained uncertain. The fatty acid amid hydrolase (FAAH), an enzyme responsible for the degradation of eCBs, has emerged as a promising target for anxiety-related disorders, since FAAH inhibitors are able to increase the levels of anandamide and thereby induce anxiolytic-like effects in rodents. The present study adopted both genetic and pharmacological approaches and tested the hypothesis that FAAH-deficient (FAAH(-/-)) mice as well as C57BL/6N mice treated with an FAAH inhibitor (URB597) would express reduced anxiety-like responses. Furthermore, as it is known that anandamide can bind several other targets than CB1 receptors, we investigated whether FAAH inhibition reduces anxiety via CB1 receptors. FAAH(-/-) mice showed reduced anxiety both in the elevated plus maze and in the light-dark test. These genotype-related differences were prevented by the CB1 receptor antagonist rimonabant (3mg/kg). Moreover, URB597 (1mg/kg) induced an anxiolytic-like effect in C57BL/6N mice exposed to the elevated plus maze, which was prevented by rimonabant (3mg/kg). The present work provides genetic and pharmacological evidence supporting the inhibition of FAAH as an important mechanism for the alleviation of anxiety. In addition, it indicates an increased activation of CB1 receptors as a mechanism underlying the effects of FAAH inhibition in two models of anxiety. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/17709120/Reduced_anxiety_like_behaviour_induced_by_genetic_and_pharmacological_inhibition_of_the_endocannabinoid_degrading_enzyme_fatty_acid_amide_hydrolase__FAAH__is_mediated_by_CB1_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(07)00214-6 DB - PRIME DP - Unbound Medicine ER -