TY - JOUR T1 - Preservation of striatal cannabinoid CB1 receptor function correlates with the anti-anxiety effects of FAAH inhibition JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.110.064196 SP - mol.110.064196 AU - Silvia Rossi AU - Valentina De Chiara AU - Alessandra Musella AU - Lucia Sacchetti AU - Cristina Cantarella AU - Maura Castelli AU - Francesca Cavasinni AU - Caterina Motta AU - Valeria Studer AU - Giorgio Bernardi AU - Benjamin F Cravatt AU - Mauro Maccarrone AU - Alessando Usiello AU - Diego Centonze Y1 - 2010/04/27 UR - http://molpharm.aspetjournals.org/content/early/2010/04/27/mol.110.064196.abstract 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 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 ER -