Mice lacking fatty acid amide hydrolase have facilitated acquisition of anandamide discriminative stimulus,

Abstract

Anandamide (AEA), an endocannabinoid (eCB), shares some, but not all, pharmacological properties with THC. This pharmacological dissociation is in part due to the rapid catabolism of AEA by fatty acid amide hydrolase (FAAH). With inhibitors of FAAH, studies have demonstrated that AEA shares THC's discriminative stimulus (DS) properties providing the leading evidence for the involvement of the eCB system in the subjective effects of marijuana. However, this remains to be fully elucidated without demonstrating that these DS effects are cross symmetrical. Thus, the current study investigated whether FAAH (−/−) mice, those lacking the ability to breakdown AEA, could be trained to discriminate AEA (6 mg/kg) versus VEH in a 2‐lever discrimination. AEA was successfully trained and dose dependently generalized. THC fully and dose dependently substituted whereas oleamide, another FAA, failed to substitute. THC's and AEA's DS effects were blocked by SR141716. This study demonstrates that: AEA's DS can be trained in FAAH (−/−) mice, THC and AEA cross generalize, and these effects are CB1 receptor mediated. Oleamide's lack of AEA‐like DS effects provides further support for the specificity of this model. Taken together, this research demonstrates that THC or AEA activation of the eCB system results in similar DS effects. Research supported by NIH grant DA‐09789.