Faah-Knockout Phenotype

Cravatt et al. (2001) generated mutant mice lacking the faah gene (FAAH / mice) and characterized by altered nociceptive threshold, enhanced memory extinction, and increased sensitivity to the effects of exogenously administered ECs (Cravatt et al., 2001 Varvel et al., 2007). Such behavioral phenotype is compatible with the higher AEA levels measured in these mice (Cravatt et al., 2001). 

In accordance with the observation reported from pharmacological studies, FAAH / mice exhibit reduced anxiety-like behavior in two experimental models, the elevated plus maze and the light-dark test (Moreira et al., 2008). Their behavioral profile in both tests is reversed by systemic administration of rimona-bant, thus suggesting that an enhancement of CBj-receptor-mediated signaling, likely due to increased AEA tone, might be responsible for the decreased anxiety in these animals. 

Discrepant observation on these mice has been reported by Naidu etal. (2007), who did not detect a phenotype of FAAH X mice in the elevated plus maze, with respect to wild-type controls. Differences in the genetic background of mice as well as in the animal housing and experimental context have been proposed as key factors determining such discrepancies (Moreira et al., 2008). 

FAAH appears as a promising target for the development of novel antianxiety and antidepressant therapies. However, several issues need to be considered. 

The first one concerns the role of other endogenous compound, such as other jV-acylethanolamides, which are also cleaved by this enzyme and can, therefore, accumulate following its pharmacological inhibition. Important biological roles 

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