Just add water: cannabinoid discrimination in a water T-maze with FAAH(−/−) and FAAH(+/+) mice

Abstract

Incomplete overlap in the discriminative stimulus effects of Δ9-tetrahydrocannabinol (THC) and the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), has been reported in food-reinforced tasks. The objective of this study was to examine cannabinoid discriminative stimulus effects in a non-appetitive procedure. Adult male mice lacking the gene for AEA’s major metabolic enzyme, fatty acid amide hydrolase (FAAH), and FAAH(+/+) mice were trained to discriminate THC or AEA in a water T-maze, in which the response was swimming to an escape platform on the injection-appropriate side. JZL184, a monoacylglycerol lipase (MAGL) inhibitor, was also tested. FAAH(−/−) mice exhibited speedier acquisition than FAAH(+/+) mice. THC and AEA fully substituted, with only minor cross-procedure potency variations. Incomplete substitution of JZL184 was observed in THC-trained FAAH(−/−) mice in the water maze task, as contrasted with full substitution in a food-reinforced nose-poke procedure. Stress-induced changes in AEA and/or 2-AG concentrations in the brain may have mediated this attenuation. JZL184 also partially substituted in AEA-trained FAAH(−/−) mice in the water maze, suggesting incomplete overlap in the stimulus effects of AEA and JZL184. Through use of a novel water maze procedure, the present study supports the work of previous behavioral pharmacologists in demonstrating robustness of the discrimination paradigm.