Pharmacological activity of fatty acid amides is regulated, but not mediated by fatty acid amide hydrolase in

Fatty acid amides (FAAs) represent a class of neuromodulatory lipids that includes the endocannabinoid anandamide and the sleep-inducing substance oleamide. Both anandamide and ole-amide produce behavioral effects indicative of cannabinoid activity, but only anandamide binds the cannabinoid (CB1) receptor in vitro. Accordingly, oleamide has been proposed to induce its behavioral effects by serving as a competitive sub-strate for the brain enzyme fatty acid amide hydrolase (FAAH) and inhibiting the degradation of endogenous anandamide. To test the role that FAAH plays as a mediator of oleamide activity in vivo, we have compared the behavioral effects of this FAA in FAAH(/) and (/) mice. In both genotypes, oleamide pro-duced hypomotility, hypothermia, and ptosis, all of which were enhanced in FAAH(/) mice, were unaffected by the CB