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Preservation of striatal cannabinoid CB1 receptor function correlates with the antianxiety effects of fatty acid amide hydrolase inhibition.
Mol Pharmacol 2010; 78(2):260-8MP

Abstract

The endocannabinoid anandamide (AEA) plays a crucial role in emotional control, and inhibition of its degradation by the fatty acid amide hydrolase (FAAH) has a potent antianxiety effect. The mechanism by which the magnification of AEA activity reduces anxiety is still largely undetermined. By using FAAH mutant mice and both intraperitoneal and intracerebroventricular administration of the FAAH inhibitor (3'-(aminocarbonyl)[1,1'-biphenyl]-3-yl)-cyclohexylcarbamate (URB597), we found that enhanced AEA signaling reversed, via central cannabinoid CB1 receptors (CB1Rs), the anxious phenotype of mice exposed to social defeat stress. This behavioral effect was associated with preserved activity of CB1Rs regulating GABA transmission in the striatum, whereas these receptors were dramatically down-regulated by stress in control animals. The hypothalamic-pituitary-adrenal (HPA) axis was not involved in the antistress effects of FAAH inhibition, although the HPA axis is a biological target of endogenous AEA. We also provided some physiological indications that striatal CB1Rs regulating GABA synapses are not the receptor targets of FAAH inhibition, which rather resulted in the stimulation of striatal CB1Rs regulating glutamate transmission. Collectively, our findings suggest that preservation of cannabinoid CB1 receptor function within the striatum is a possible synaptic correlate of the antianxiety effects of FAAH inhibition.

Authors+Show Affiliations

Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

20424126

Citation

Rossi, Silvia, et al. "Preservation of Striatal Cannabinoid CB1 Receptor Function Correlates With the Antianxiety Effects of Fatty Acid Amide Hydrolase Inhibition." Molecular Pharmacology, vol. 78, no. 2, 2010, pp. 260-8.
Rossi S, De Chiara V, Musella A, et al. Preservation of striatal cannabinoid CB1 receptor function correlates with the antianxiety effects of fatty acid amide hydrolase inhibition. Mol Pharmacol. 2010;78(2):260-8.
Rossi, S., De Chiara, V., Musella, A., Sacchetti, L., Cantarella, C., Castelli, M., ... Centonze, D. (2010). Preservation of striatal cannabinoid CB1 receptor function correlates with the antianxiety effects of fatty acid amide hydrolase inhibition. Molecular Pharmacology, 78(2), pp. 260-8. doi:10.1124/mol.110.064196.
Rossi S, et al. Preservation of Striatal Cannabinoid CB1 Receptor Function Correlates With the Antianxiety Effects of Fatty Acid Amide Hydrolase Inhibition. Mol Pharmacol. 2010;78(2):260-8. PubMed PMID: 20424126.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preservation of striatal cannabinoid CB1 receptor function correlates with the antianxiety effects of fatty acid amide hydrolase inhibition. AU - Rossi,Silvia, AU - De Chiara,Valentina, AU - Musella,Alessandra, AU - Sacchetti,Lucia, AU - Cantarella,Cristina, AU - Castelli,Maura, AU - Cavasinni,Francesca, AU - Motta,Caterina, AU - Studer,Valeria, AU - Bernardi,Giorgio, AU - Cravatt,Benjamin F, AU - Maccarrone,Mauro, AU - Usiello,Alessandro, AU - Centonze,Diego, Y1 - 2010/04/27/ PY - 2010/4/29/entrez PY - 2010/4/29/pubmed PY - 2010/8/4/medline SP - 260 EP - 8 JF - Molecular pharmacology JO - Mol. Pharmacol. VL - 78 IS - 2 N2 - The endocannabinoid anandamide (AEA) plays a crucial role in emotional control, and inhibition of its degradation by the fatty acid amide hydrolase (FAAH) has a potent antianxiety effect. The mechanism by which the magnification of AEA activity reduces anxiety is still largely undetermined. By using FAAH mutant mice and both intraperitoneal and intracerebroventricular administration of the FAAH inhibitor (3'-(aminocarbonyl)[1,1'-biphenyl]-3-yl)-cyclohexylcarbamate (URB597), we found that enhanced AEA signaling reversed, via central cannabinoid CB1 receptors (CB1Rs), the anxious phenotype of mice exposed to social defeat stress. This behavioral effect was associated with preserved activity of CB1Rs regulating GABA transmission in the striatum, whereas these receptors were dramatically down-regulated by stress in control animals. The hypothalamic-pituitary-adrenal (HPA) axis was not involved in the antistress effects of FAAH inhibition, although the HPA axis is a biological target of endogenous AEA. We also provided some physiological indications that striatal CB1Rs regulating GABA synapses are not the receptor targets of FAAH inhibition, which rather resulted in the stimulation of striatal CB1Rs regulating glutamate transmission. Collectively, our findings suggest that preservation of cannabinoid CB1 receptor function within the striatum is a possible synaptic correlate of the antianxiety effects of FAAH inhibition. SN - 1521-0111 UR - https://www.unboundmedicine.com/medline/citation/20424126/Preservation_of_striatal_cannabinoid_CB1_receptor_function_correlates_with_the_antianxiety_effects_of_fatty_acid_amide_hydrolase_inhibition_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=20424126 DB - PRIME DP - Unbound Medicine ER -