Title

 

Authors

S. Di Serio, V. Dainese, D. Guaraldi, M. G. Scrocco, A. Caprioli, F. Borsini

Sigma-Tau  Industrie Farmaceutiche Riunite S.p.a., Pomezia - Roma, Italia.

 

Abstract

Many animal models of anxiety are based on the principle of innate general avoidance behaviors. One of them is the elevated plus maze (EPM) [Hogg, 1996], a model based on the natural aversion of rodents for open spaces that exploits the conflict between exploration of, and aversion to, elevated open space. The provoked behavior profiles in the EPM appear to include elements of neophobia, exploration and approach/avoidance conflict. EPM is able to demonstrate anxiolytic (benzodiazepinic)-like effects of drugs. Anandamide and 2-arachidonoyl glycerol, referred to as endocannabinoids, are the endogenous agonists for the cannabinoid receptor CB1. Several studies support a role for endocannabinoids in the attenuation of anxiety-related behaviors (Piomelli, 2003). The fatty acid amide hydrolase (FAAH), an enzyme responsible for the degradation of endocannabinoids, is a potential target for anxiety-related disorders, since FAAH inhibitors increase anandamide levels and induce anxiolytic-like effects in rodents (Kathuria et al., 2003). The purpose of the present study was to evaluate the effects of the new FAAH inhibitor, ST4070, on anxiety-like behavior in the elevated plus maze. ST4070, at oral dose of 30 mg/kg, but not at 3 and 10 mg/kg, let mice to spend longer time in open arms without affecting number of entrances into the open arms, number of total entrances and total distance walked, compared to control group. Diazepam, at intraperitoneal dose of 1 mg/kg, induced mice to spend longer time in open arms and to walk more, but did not induced changes in the number of entrances into the open arms or the number of total entrances, compared to control group. These results suggest that ST4070 reduces anxiety-like behavior in mouse evaluated in elevated plus maze.
 
Hogg (1996). Pharmacology Biochemistry and Behavior. 54, 21-30.
Piomelli (2003). Nature Reviews Neuroscience. 4, 873-884.
Kathuria et al. (2003). Nature Medicine. 9, 76-81.