• Article

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

Incomplete overlap in the discriminative stimulus effects of Δ9-tetrahydrocannabinol (THC) and the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol has been reported in food-reinforced tasks. The aim of this study was to examine cannabinoid discriminative stimulus effects in a nonappetitive 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 inhibitor, was also tested. FAAH(−/−) mice showed faster 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-arachidonoylglycerol 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 the use of a novel water-maze procedure, the present study supports the work of previous behavioral pharmacologists in showing the robustness of the discrimination paradigm.

Citation

Wiley, J., Lefever, T., Pulley, N., Marusich, J., Cravatt, BF., & Lichtman, AH. (2016). Just add water: cannabinoid discrimination in a water T-maze with FAAH(−/−) and FAAH(+/+) mice. Behavioural Pharmacology, 27(5), 479-484. https://doi.org/10.1097/FBP.0000000000000228