RT Journal Article
SR Electronic
T1 Preservation of striatal cannabinoid CB1 receptor function correlates with the anti-anxiety effects of FAAH inhibition
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP mol.110.064196
DO 10.1124/mol.110.064196
A1 Silvia Rossi
A1 Valentina De Chiara
A1 Alessandra Musella
A1 Lucia Sacchetti
A1 Cristina Cantarella
A1 Maura Castelli
A1 Francesca Cavasinni
A1 Caterina Motta
A1 Valeria Studer
A1 Giorgio Bernardi
A1 Benjamin F Cravatt
A1 Mauro Maccarrone
A1 Alessando Usiello
A1 Diego Centonze
YR 2010
UL http://molpharm.aspetjournals.org/content/early/2010/04/27/mol.110.064196.abstract
AB 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 anti-anxiety effect. The mechanism by which 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 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 anti-stress effects of FAAH inhibition, although 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 anti-anxiety effects of FAAH inhibition.The American Society for Pharmacology and Experimental Therapeutics